Insecticial 3-(2,6-disubstituted phenyl)-5-[4- or 5-arylthien-2- or -3-yl]-1,2,4-triazoles

ABSTRACT

Triazole compounds having a 2,6-disubstituted-phenyl group in the 3-position, arylthien-2- or -3-yl in the 5-position and an alkyl group in the 1-position are effective in controlling lepidoptera, coleoptera, mites and other sucking pests.

This application claims the benefit of U.S. Provisional Application No.60/322,236, filed Sep. 14, 2001.

BACKGROUND OF THE INVENTION

The present invention concerns novel 3-(2,6-disubstituted phenyl)-5-(4-or 5-arylthien-2- or -3-yl)-1,2,4-triazoles and their use in controllinglepidoptera, coleoptera, mites and other sucking pests. This inventionalso includes new synthetic procedures, intermediates for preparing thecompounds, pesticide compositions containing the compounds, and methodsof controlling lepidoptera, coleoptera, mites and sucking pests usingthe compounds.

There is an acute need for new insecticides and acaricides. Insects andmites are developing resistance to the insecticides and acaricides incurrent use. At least 400 species of arthropods are resistant to one ormore insecticides. The development of resistance to some of the olderinsecticides, such as DDT, the carbamates, and the organophosphates, iswell known. But resistance has even developed to some of the newerpyrethroid insecticides and acaricides. Therefore a need exists for newinsecticides and acaricides, and particularly for compounds that havenew or a typical modes of action.

A number of 3,5-diphenyl-1H-1,2,4-triazole derivatives have beendescribed in the literature as having acaricidal activity (U.S. Pat. No.5,482,951; JP 8092224, EP 572142, JP 08283261). U.S. Pat. No. 6,015,826discloses certain 3-(substituted phenyl)-5-(thienyl)-1,2,4-triazoles andtheir use in controlling certain insects and mites, viz., aphids, mitesand whiteflies. The present invention provides novel compounds withbroad-spectrum activity against lepidoptera and coleoptera in additionto mites and other sucking pests.

SUMMARY OF THE INVENTION

This invention concerns compounds especially useful for the control oflepidoptera, coleoptera, mites and other sucking pests. Morespecifically, the invention concerns compounds of the formula (1)

wherein

Q represents

X and Y independently represent Cl or F;

R¹ and R² independently represent H, C₁-C₆ alkyl or halogen, providedthat when Q is Q¹ or Q³, then R¹ and R² are not both H;

R³ represents C₁-C₃ alkyl;

R⁴ represents halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ thioalkyl, C₃-C₆alkoxyalkoxy, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy, C₁-C₆ halothioalkyl,C₃-C₆ alkenyloxy, or phenoxy;

R⁵ represents H, halogen or a C₁-C₆ alkyl ether or haloalkyl ether,which, when taken together with R⁴, forms a 5- or 6-membered ringcontaining 1 or 2 oxygen atoms;

or a phytologically acceptable acid addition salt thereof.

Preferred compounds of formula (1) include the following classes:

(1) Compounds of formula (1) wherein X and Y are both F.

(2) Compounds of formula (1) wherein X and Y are both Cl.

(3) Compounds of formula (1) wherein X is F and Y is Cl (morepreferred).

(4) Compounds of formula (1) wherein Q is Q¹ or Q³.

(5) Compounds of formula (1) wherein Q is Q².

(6) Compounds of formula (1) wherein R¹ is CH₃, CH₂CH₃ or Cl when Q isQ¹ or Q³, more preferably R¹ is CH₃.

(7) Compounds of formula (1) wherein R¹ is H, CH₃, CH₂CH₃, Cl or Br whenQ is Q², more preferably R¹ is H or CH₃.

(8) Compounds of formula (1) wherein R² is H, CH₃, CH₂CH₃, Cl or Br,more preferably R² is H or CH₃.

(9) Compounds of formula (1) wherein R⁴ is F, Cl, CF₃, haloalkoxy orphenoxy, more preferably R⁴ is haloalkoxy.

(10) Compounds of formula (1) wherein R⁴ is in the 4-position of thephenyl ring.

(11) Compounds of formula (1) wherein R⁵ is H, F, Cl, or CF₃.

(12) Compounds of formula (1) wherein R³ is CH₃.

It will be appreciated by those skilled in the art that the mostpreferred compounds are generally those which are comprised ofcombinations of the above preferred classes.

The invention also provides new processes and intermediates forpreparing compounds of formula (1) as well as new compositions andmethods of use, which will be described in detail hereinafter.

DETAILED DESCRIPTION OF THE INVENTION

Throughout this document, all temperatures are given in degrees Celsius,and all percentages are weight percentages unless otherwise stated.

Unless specifically limited otherwise, the terms “alkyl” and “alkenyl”,as well as derivative terms such as “alkoxy”, “alkenyloxy” and“thioalkyl”, as used herein, include within their scope straight chain,branched chain and cyclic moieties. The term “alkenyl” is intended toinclude one or more unsaturated bonds.

Unless specifically limited otherwise, the term “halogen”, as well asderivative terms such as “halo”, as used herein, refers to fluorine,chlorine, bromine, and iodine. Preferred halogens are fluorine andchlorine.

The terms “haloalkyl” and “haloalkenyl” refer to alkyl and alkenylgroups substituted with from one up to the maximum possible number ofhalogen atoms. The terms “haloalkoxy” and “halothioalkyl” refer toalkoxy and thioalkyl groups substituted with from one up to the maximumpossible number of halogen atoms.

The term “alkoxyalkoxy” refers to an alkoxy group substituted with analkoxy group. The term “alkyl ether” refers to an alkylene oxide groupwhich can be bonded either through the carbon or the oxygen atom.

Unless otherwise indicated, when it is stated that a group may besubstituted with one or more substituents selected from an identifiedclass, it is intended that the substituents may be independentlyselected from the class.

Synthesis

Compounds of formula (1) can be prepared by the methods illustrated inScheme A:

wherein X, Y, R¹, R², R³, R⁴ and R⁵ are defined as in formula (1).

In step a of Scheme A, the compound of formula (A) is coupled with theacid chloride of formula (B) to provide acyl thioimidate of formula (C).Pyridine is the preferred base for coupling, however any organic orinorganic base can be used. Acid chlorides of formula (B) are preparedfrom corresponding carboxylic acids of formula (G)

which are either commercially available or are readily made throughknown procedures.

Thioimidates (A) are readily available through alkylation of thecorresponding thioamides (H) which themselves are commercially availableor can be made from the amide (Phosphorus Sulfur, 1985, 25, 297-305) ornitrile (Chem.-Ztg. 1980, 104, 365; J. Chem. Soc. 1952, 742; Can. J.Chem. 1985, 63, 3075).

In the cyclization step b of Scheme A, the compound of formula (C) canbe reacted with hydrazine or a substituted hydrazine in toluene at 25 to110° C. to afford the triazole intermediate (D) in good yield with ahigh degree of regiospecificity. Instead of toluene other aproticsolvents such as tetrahydrofuran (THF) can also be used.

In step c of Scheme A, the compound of formula (D) can be brominatedwith bromine in acetic acid in the presence or absence of sodium acetateat 25° C. to refluxing temperature to afford the compound of formula(E).

In the Suzuki coupling step d of Scheme A, the compound of formula (E)can be reacted with an appropriately substituted R⁴/R⁵—boronic acid toprovide the compound of formula (F). The coupling can be carried out inan acetonitrile/water mixture or ethanol, at a temperature in the rangefrom ambient to refluxing. Catalytic amounts ofdichlorobis(triphenylphosphine)palladium(II) ortetrakis(triphenylphosphine)palladium(0) are typically used forcoupling, however other Pd(II) or Pd(0) catalysts can also be used.Typically sodium carbonate is used as a base in the reaction, howeverother inorganic bases such as potassium carbonate or organic bases suchas triethylamine can also be used.

Alternatively, compounds of formula (1) can also be prepared by themethods illustrated in Scheme B:

wherein X, Y, R¹, R², R³, R⁴ and R⁵ are defined as in formula (1).

In step a of Scheme B, the compound of formula (A) is coupled with theacid chloride of formula (B′) to provide acyl thioimidate of formula(C′) in a similar fashion as described for step a in Scheme A. Acidchlorides of formula (B′) are prepared from corresponding carboxylicacids of formula (G′)

which are readily made through known procedures.

The cyclization step b of Scheme B is performed in a similar fashion asstep b of Scheme A to afford the triazole intermediate (E) in good yieldwith a high degree of regioselectivity.

In step c of Scheme B, the Suzuki coupling was performed in a similarfashion as step d of Scheme A to afford the compound of formula (F).

Alternatively, compounds of formula (1) can also be prepared by themethods illustrated in Scheme C:

wherein X, Y, R¹, R², R³, R⁴ and R⁵ are defined as in formula (1).

In step a of Scheme C, the compound of formula (A) is coupled with theacid chloride of formula (B″) to provide acyl thioimidate of formula(C″) in a similar fashion as described for step a in Scheme A. Acidchlorides of formula (B″) are prepared from corresponding carboxylicacids of formula (G″)

which are readily made through known procedures.

The cyclization step b of Scheme C is performed in a similar fashion asstep b of Scheme B to afford the triazole (F).

EXAMPLES Example A

2,4-Dimethylthioiphene-3-Carboxylic Acid

n-Butyllithium (2.5 M in hexanes, 18.6 mL, 46 mmol) was added to apre-cooled solution of 4-methylthiophene-3-carboxylic acid (3.0 g, 21mmol) in dry tetrahydrofuran (THF, 35 mL) at 62° C. The reaction mixturewas stirred at −78° C. for an hour, allowed to warm to −40° C. andre-cooled to −78° C. before adding iodomethane (3.28 mL, 7.49 g, 53mmol). After addition, the reactants were stirred at −78° C. for an hourand then allowed to warm to room temperature over 14 hours and quenchedwith water (20 mL). The organic phase was extracted with dilute sodiumhydroxide (0.2 N, 3×30 mL). The combined aqueous extracts were washedwith ether (2×30 mL), cooled in an ice bath and acidified to pH 3 usingconcentrated hydrochloric acid. The resultant precipitate was extractedwith ether (3×50 mL). The combined ethereal extracts were washed withwater (50 mL) and brine (50 mL), dried over magnesium sulphate,concentrated under reduced pressure and recrystallised from ethylacetate/hexane to give product as an amorphous white solid (2.7 g, 82%):mp 164-165° C.; ¹H NMR (CDCl₃) δ 6.65 (q, 1H), 2.73 (s, 3H), 2.43 (d,3H); EI/MS 156 m/e (M+); IR (liq film) 1664 cm⁻¹; Calcd for C₇H₈O₂S: C,53.8; H, 5.16; Found: C, 53.8; H, 5.11.

Example B

5-Bromo-2,4-dimethylthiophene-3-Carboxylic Acid

A solution of bromine (0.73 mL, 2.25 g, 14 mmol) in glacial acetic acid(8 mL) was added to a solution of 2,4-dimethylthiophene-3-carboxylicacid (2.1 g, 13 mmol) in glacial acetic acid (24 mL) at 6° C. Uponcompletion, the reaction was stirred at 10° C. for an hour, diluted withglacial acetic acid (30 mL), stirred for 14 hours at room temperature,poured into water (400 mL) and extracted with ether (3×40 mL). Thecombined ethereal extracts were extracted with dilute sodium hydroxide(0.2 N, 3×30 mL). The combined basic extracts were cooled in an ice bathand then acidified to pH 3 using concentrated hydrochloric acid.Precipitated solids were extracted with ether (3×40 mL). Pooled organicextracts were washed with water (50 mL) and brine (50 mL), dried overmagnesium sulphate and concentrated under reduced pressure. The residuewas recrystallised from ethyl acetate/hexane to give product as anamorphous white solid (2.7 g, 85%): mp 183-184° C.; ¹H NMR (CDCl₃) δ2.67 (s, 3H), 2.38 (s, 3H); EI/MS 235 m/e (M⁺); IR (liq film) 1674 cm⁻¹;Calcd. for C₇H₇BrO₂S: C, 35.8; H, 3.00; S, 13.6; Found: C, 35.8; H,2.99; N, 13.5.

Example C

Ethyl 4,5-dibromo-3-chlorothiophene-2-carboxylate

Ethyl 3-chlorothiophene-2-carboxylate (3.96 g, 20.7 mol) in a suspensionof sodium acetate (12.71 g, 154 mmol) and glacial acetic acid (35 mL)was treated with bromine (9.6 mL, 186.3 mmol). The reaction mixture wasstirred at 75° C. under N₂ for 136 hours and then at 25° C. for 144hours. The reaction mixture was poured onto ice cold satd aq sodiumbicarbonate and aq sodium metabisulfite. The mixture was stirred withether (100 mL) for 30 minutes. Extraction with ether (3×150 mL) gave anorganic layer that was washed with water (150 mL) and satd aq sodiumchloride (150 mL), dried over magnesium sulfate and concentrated to giveproduct as a white solid (5.83 g, 80%): mp 58-63° C.; ¹H NMR (CDCl₃) δ4.37 (q, 2H, J=7.1 Hz), 1.38 (t, 3H, J=7.1 Hz,); EI/MS 347 m/e (M⁺).

Example D

4,5-Dibromo-3-chlorothiophene-2-Carboxylic Acid

Ethyl 4,5-dibromo-3-chlorothiophene-2-carboxylate (5.52 g, 15.8 mmol)and lithium hydroxide (0.716 g, 31.7 mmol) were taken up in mixture ofTHF (30 mL) and water (30 mL). The reaction mixture was stirred at 25°C. for 32 hours. The aqueous layer was made acidic by the dropwiseaddition of conc hydrochloric acid and extracted with ether (3×50 mL).The combined organic extracts were dried over sodium sulfate, filteredand concentrated to give the product as a white solid (4.38 g, 86%) thatwas used without purification: mp 209-223° C. (d); ¹H NMR (CDCl₃ andDMSO-d₆) δ 4.15 (bs, 1H); EI/MS 320 m/e (M⁺).

Example E

Methyl2-chloro-6-fluoro-N-[(4-methylthien-3-yl)carbonyl]benzenecarbimidothioate

To a suspension of 4-methylthiophene-3-carboxylic acid (2.74 g, 19 mmol)in 1,2-dichloroethane (DCE, 100 mL) was added thionyl chloride (5.67 mL,9.25 g, 78 mmol) and dimethylformamide (DMF, 10 drops from a Pasteurpipette). After refluxing under nitrogen for 4 hours, the reactionmixture was concentrated under reduced pressure. The residue was takenup in DCE (80 mL) and concentrated once again under reduced pressure.This residue was dissolved in DCE (30 mL) and added at a dropwise rateinto a suspension of S-methylthio-2-chloro-6-fluorobenzamidinium bromide(5.5 g, 19 mmol) in DCE (50 mL) at −3° C. Upon completion, a solution ofdry pyridine (4.72 mL, 4.61 g, 58 mmol) in DCE (3 mL) was added at arate required to maintain the temperature below 0° C. The reaction wasallowed to come to room temperature over 14 hours, washed with water(100 mL), saturated aqueous sodium carbonate (100 mL) and brine (70 mL),dried over magnesium sulphate and concentrated under reduced pressure toleave a thick, yellow liquid which solidified upon standing at roomtemperature for several hours (4.33 g, 68%): ¹H NMR (CDCl₃) δ 8.09 (d,1H), 7.27-7.32 (m, 1H), 7.16 (d, 1H), 7.00 (t, 1H), 6.87 (d, 1H), 2.58(s, 3H), 2.34 (s, 3H); EI/MS: 327 m/e (M−1); IR (liq film) 1669, 1612and 1599 cm⁻¹.

The following compounds were prepared according to the general procedureof Example E.

Methyl2-chloro-N-[(4.5-dibromo-3-chlorothien-2-yl)carbonyl]-6-fluorobenzene-carbimidothioate

Product was isolated as a burnt orange solid (73% yield): mp 111-118°C.; ¹H NMR (CDCl₃) δ 7.32 (ddd, 1H, J=5.8, 8.0, 8.4 Hz), 7.19 (d, 1H,J=8.0 Hz), 7.03 (ddd, 1H, J=0.85, 8.0, 8.4 Hz) 2.65 (s, 3H); EI/MS 470m/e (M−Cl).

Methyl2-chloro-N-[(4-chlorothien-3-yl)carbonyl]-6-fluorobenzenecarbimidothioate

Product was isolated as a dark brown liquid that turned to a waxy solidover time (85% yield): ¹H NMR (CDCl₃) δ 8.12 (d, 1H, J=3.6 Hz),7.33-7.25 (m, 2H), 7.18 (dd, 1H, J=1.09, 0.73 Hz), 7.14 (d, 1H, J=3.6Hz), 7.03 (dd, 1H, J=1.09, 8.4 Hz), 2.60 (s, 3H); EI/MS 348 m/e (M⁺).

Example F

3-(2-Chloro-6-fluorophenyl)-1-methyl-5-(4-methylthien-3-yl)-1H-1,2,4-triazole

A solution of methylhydrazine (2.02 mL, 1.75 g, 38 mmol) in toluene (5mL) was added at a rapid dropwise rate to a solution of methyl2-chloro-6-fluoro-N-[(4-methylthien-3-yl)carbonyl]benzenecarbimidothioate (4.15 g, 12.7 mmol) in dry toluene (100mL) at 55° C. The reaction was stirred at this temperature for 10minutes and then left at room temperature for 14 hours. Anotheridentical portion of methylhydrazine in toluene was added at roomtemperature and the reaction was heated at 80° C. for 3 hours andrefluxed for an additional 3 hours. After cooling to room temperature,the reaction mixture was washed with water (100 mL), dilute hydrochloricacid (0.05 N, 2×100 mL) and brine (70 mL), dried over magnesium sulphateand concentrated under reduced pressure. The residue was recrystallisedfrom ethyl acetate/hexane to give white cubes. The mother liquor waschromatographed (eluant, 30:9:1 hexane/methylene chloride/acetonitrileto afford the product (3.25 g, 84%): mp 153-155° C.; ¹H NMR (CDCl₃) δ7.54 (d, 1H), 7.26-7.38 (m, 2H), 7.06-7.13 (m, 2H), 3.98 (s, 3H), 2.35(d, 3H); ¹⁹F NMR (external reference)—110 ppm; EI/MS 307 m/e (M−1).

The following compounds were prepared according to the general procedureof Example F.

3-(2-Chloro-6-fluorophenyl)-5-(4,5-dibromo-3-chlorothien-2-yl)-1-methyl-1H-1,2,4-triazole

Product was isolated as a tan solid (24% yield): mp 180-182° C.; ¹H NMR(CDCl₃) δ 7.40-7.27 (m, 2H), 7.14-7.08 (m, 1H), 4.03 (s, 3H); EI/MS 485m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-(4-chlorothien-3-yl)-1-methyl-1H-1,2,4-triazole

Product was isolated as a tan solid (28% yield): mp 126-133° C.; ¹H NMR(CDCl₃) δ 7.72 (d, 1H, J=3.6 Hz), 7.39-7.28 (m, 3H), 7.13-7.07 (m, 1H),3.96 (s, 3H); EI/MS 327 m/e (M⁺); Calcd for C₁₃H₁₈Cl₂FN₃S: C, 47.58; H,2.46; N, 12.80; S, 9.77; Found: C, 47.45; H, 2.40; N, 12.56; S, 9.51.

Example G

3-(2-Chloro-6-fluorophenyl)-(5-bromo-4-methylthien-3-yl)-1-methyl-1H-1,2,4-triazole

A suspension of3-(2-chloro-6-fluorophenyl)-1-methyl-5-(4-methylthien-3-yl)-1H-1,2,4-triazole(2.35 g, 7.6 mmol) in glacial acetic acid (15 mL) was heated to 45° C.in order to effect solubilization. After cooling to 10° C., a solutionof bromine (1.34 g, 0.43 mL, 8.4 mmol) in glacial acetic acid (4 mL) wasadded and the thick gel formed was stirred for 14 hours at roomtemperature. The reaction mixture was poured into cold water (100 mL)and extracted with ether (3×70 mL). The combined ethereal extracts werewashed with water (100 mL), saturated aqueous sodium bicarbonate (2×100mL), aqueous sodium bisulphite (10% solution, 300 mL) and brine (100mL), dried over magnesium sulphate and concentrated under reducedpressure. Recrystallisation from ethyl acetate/hexane afforded yellowcubes. The mother liquor was chromatographed over silica gel to affordthe product as colorless cubes (2.6 g, 89%): mp 133-134° C.; ¹H NMR(CDCl₃) δ 7.51 (s, 1H), 7.29-7.39 (m, 2H), 7.11 (t, 1H), 3.98 (s, 3H),2.27 (s, 3H); EI/MS 386 m/e (M⁺).

The following compounds were prepared according to the general procedureof Example G.

3-(2,6-Difluoronhenyl)-5-(5-bromo-3-chlorothien-2-yl)-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (51% yield): mp 134-137° C.; ¹HNMR (CDCl₃) δ 7.43-7.33 (m, 1H), 7.08 (s, 1H), 7.06-6.98 (m, 2H), 4.02(s, 3H); EI/MS 391 m/e (M+H); Calcd for C₁₃H₇BrClF₂N₃S: C, 39.97; H,1.81; N, 10.76; S, 8.21; Found: C, 39.74; H, 1.82; N, 10.54; S, 8.27.

3-(2-Chloro-6-fluorophenyl)-5-(5-bromo-4-chlorothien-3-yl)-1-methyl-1H-1,2,4-triazole

Product was isolated as a light yellow solid (51% yield): mp 111-117°C.; ¹H NMR (CDCl₃) δ 7.71 (s, 1H), 7.39-7.29 (m, 2H), 7.14-7.08 (m, 1H),3.97 (s, 3H); EI/MS 407 m/e (M⁺); Calcd for C₁₃H₇BrCl₂FN₃S: C, 38.36; H,1.73; N, 10.32; Found: C, 38.57; H, 1.71; N, 10.18.

Example H

3-(2-Chloro-6-fluorophenyl)-5-(4-bromo-3,5-dimethylthien-2-yl)-1-methyl-1H-1,2,4-triazole

n-Butyllithium (0.7 g, 10.8 mmol) was added dropwise to a solution of5-(4,5-dibromo-3-methylthien-2-yl)-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole(5 g, 10.8 mmol) in THF (70 mL) at −70° C. and stirred for 1 hour.Iodomethane (1.6 g, 11.29 mmol) was added to the reaction mixture andallowed to warm to 25° C. After adding saturated aq ammonium chloride(10 mL), the organic layer was separated, washed with water, followed bysaturated aq sodium chloride (20 mL) and dried over sodium sulfate,filtered, and concentrated. The residue was chromatographed to give theproduct as a yellow oil (2.0 g, 47%): ¹H NMR (CDCl₃) δ 2.32 (s, 3H),2.48 (s, 3H), 3.99 (s, 3H), 7.07-7.13 (m, 1H), 7.28-7.38 (m, 2H); EI/MS400 m/e (M⁺); Calcd. for C₁₅H₁₂ClBrFN₃S: C, 44.96; H, 3.02; N, 10.49;Found: C, 44.94; H, 3.01; N, 10.29.

Example I

2-Fluoro-4-trifluoromethoxybenzeneboronic Acid

To a solution of n-butyllithium (2.5 M solution in hexanes, 14.1 mL) inTHF (30 mL) at −98° C. was added a solution of4-bromo-3-fluorotrifluoromethoxy-benzene in THF (3 mL). After stirringfor 10 min. at −98° C., triisopropyl borate (4.88 mL, 3.98 g, 21 mmol)was added at a rate needed to keep the temperature below −97° C. Thereaction mixture was allowed to warm to −30° C. over 30 minutes,re-cooled to −78° C. and stirred at this temperature for 30 min.Concentrated hydrochloric acid (2 mL) was added and the reaction mixturewas concentrated under reduced pressure. Dilute hydrochloric acid (0.2N, 15 mL) was added and the mixture was extracted with ether (3×20 mL).The combined ethereal layers were extracted with dilute sodium hydroxide(0.02 N, 3×30 mL). The combined aqueous extracts were cooled to 0° C.,acidified to pH 3.5 using concentrated hydrochloric acid and extractedwith ether (3×30 mL). The combined ethereal layers were then washed withwater (15 mL) and brine (15 mL), dried over magnesium sulphate andconcentrated under reduced pressure to leave 2.3 g of yellow solid.Recrystallisation from hexane afforded pink needles (1.25 g, 41%): mp89-93° C.; ¹H NMR (CDCl₃) δ 7.89 (t, 1H), 7.07 (d, 1H), 6.94 (d, 1H),5.11 (d, 2H); EI/MS 223 m/e (M−1).

The following compounds were prepared according to the general procedureof Example I.

2-Fluoro-4-trifluoromethylbenzeneboronic Acid

Product was isolated as a yellow solid (30% yield): mp 115-116° C.; ¹HNMR (CDCl₃) δ 7.98 (t, 1H), 7.47 (d, 1H), 7.32 (d, 1H), 5.11 (d, 1H);EI/MS 207 m/c (M−1); IR (liq film) 1331 cm⁻¹.

2-Fluoro-5-trifluoromethylbenzeneboronic Acid

Product was isolated as iridescent plates (24% yield): ¹H NMR (CDCl₃) δ7.61 (m, 1H), 7.51 (m, 1H), 7.04 (m, 1H), 5.11 (d, 1H); EI/MS 207 m/e(M−1); IR (liq film) 1361 cm⁻¹; Calcd. for C₇H₅BF₄O₂: C, 40.44; H, 2.42;Found: C, 39.79; H, 2.33.

Example J

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,1,2,2-tetrafluoroethoxybenzene

Triethylamine (4.59 mL, 3.33 g, 33 mmol) and4-(1,1,2,2-tetrafluoroethoxy)bromobenzene (3 g, 11 mmol) were added to asuspension of 1,1′-bis-[diphenylphosphino]ferrocenedichloropalladium(II) in dry dioxane (45 mL). Neat 4,4,5,5-tetramethyl-1,3,2-dioxaborane(2.39 mL, 2.11 g, 16 mmol) was then added to this mixture and refluxedfor three days. After cooling to room temperature, the reaction mixturewas poured into water (300 mL) and extracted with ether (3×100 mL). Thecombined ethereal extracts were washed with water (150 mL) and brine (70mL), dried over magnesium sulphate, concentrated under reduced pressureand distilled at 0.06 mm Hg (99° C.) to afford the product (1.88 g, 53%)as a yellow oil: ¹H NMR (CDCl₃) δ 7.83 (d, 2H), 7.20 (d, 2H), 6.08, 5.90& 5.72 (tt, 1H), 1.34 (s, 12H); EI/MS 320 m/e (M⁺); IR (liq film) 1364cm⁻¹.

Example 1

3-(2-Chloro-6-fluorolphenyl)-5-[4-methyl-5-(4-trifluoromethoxyphenylthien-3-yl]-1-methyl-1H-1,2,4-triazole

A mixture of 4-trifluoromethoxybenzeneboronic acid (0.4 g, 1.1 mmol),3-(2-chloro-6-fluorophenyl)-5-[5-bromo-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole(0.4 g, 1 mmol), sodium carbonate (0.2 g, 1.9 mmol),tri-o-tolylphosphine (32 mg, 0.1 mmol) anddichlorobis(triphenylphosphine)palladium(II) (73 mg, 0.1 mmol) wererefluxed under nitrogen for 16 hours in an acetonitrile (14 mL) andwater (1.4 mL) solution. After cooling to room temperature, thereactants were poured into dilute hydrochloric acid (1 N, 50 mL) andextracted with ether (3×50 mL). The combined ethereal extracts werewashed with water (100 mL), saturated aqueous bicarbonate (70 mL) andbrine (50 mL), dried over magnesium sulphate, filtered and concentrated.The residue was chromatographed over silica to afford the product as ayellow gum (210 mg, 43%): ¹H NMR (CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H),7.28-7.39 (m, 4H), 7.11 (t, 1H), 4.03 (s, 3H), 2.33 (s,3H); EI/MS 467m/e (M−1).

The following compounds were prepared according to the general procedureof Example 1.

3-(2-Chloro-6-fluorophenyl)-5-{4-chloro-5-[4-(trifluoromethoxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid: mp 112-116° C.; ¹H NMR (CDCl₃) δ7.72 (t, 3H, J=4.3 Hz), 7.40-7.30 (m, 4H), 7.15-7.09 (m, 1H), 4.09 (s,3H); EI/MS 487 m/e (M⁺); Calcd for C₂₀H₁₁Cl₂F₄N₃OS: C, 49.20; H, 2.27;N, 8.61; Found: C, 48.95; H, 2.24; N, 8.48.

3-(2-Chloro-6-fluorophenyl)-5-{4-chloro-5-[4-(trifluoromethyl)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (66% yield): mp 88-92° C.; ¹H NMR(CDCl₃) δ 7.82 (d, 2H, J=8.0 Hz), 7.76 (s, 1H), 7.74 (d, 2H, J=8.0 Hz),7.40-7.30 (m, 2H), 7.15-7.09 (m, 1H), 6.96-6.92 (m, 1H), 4.02 (m, 3H);EI/MS 471 m/e (M⁺); Calcd for C₂₀H₁₁Cl₂F₄N₃S: C, 50.86; H, 2.35; N,8.90; Found: C, 50.81; H, 2.39; N, 8.77.

3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a light yellow solid (77% yield): mp 120-128°C.; ¹H NMR (CDCl₃) δ 7.63-7.58 (m, 3H), 7.39-7.29 (m, 2H), 7.14-7.08 (m,1H), 7.01-6.96 (m, 2H), 4.09 (q, 2H, J=6.9 Hz), 4.00 (s, 3H), 1.45 (t,3H, J=6.9 Hz); EI/MS 447 m/e (M⁺).

3-(2,6-Difluorophenyl)-5-[5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellowish solid (37% yield): mp 88-91° C.; ¹HNMR (CDCl₃) δ 7.75 (d, 1H), 7.72 (d, 1H), 7.67 (d, 2H), 7.36-7.43 (m,1H), 7.02 (t, 1H), 4.17 (s, 3H); EI/MS 437 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (88% yield): mp 124-125° C.; ¹HNMR (CDCl₃) δ 7.77 (d, 1H), 7.74 (d, 1H), 7.67 (d, 2H), 7.25-7.40 (m,4H), 7.11 (t, 1H), 4.19 (s, 3H); EI/MS: 453 m/e (M−1); Calcd. forC₂₀H₁₂ClF₄N₃OS: C, 52.9; H, 2.67; N, 9.26; S, 7.06; Found: C, 53.1; H,2.67; N, 8.7; S, 7.0.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an amorphous white solid (32% yield): mp 121°C.; ¹H NMR (CDCl₃) δ 8.02 (s, 1H), 7.89 (s, 1H), 7.82 (t, 1H), 7.47 (s,1H), 7.43 (d, 1H), 7.29-7.39 (m, 2H), 7.11 (t, 1H), 4.19 (s, 3H); EI/MS:471 m/e (M−1); Calcd. for C₂₁H₁₅ClF₅N₃S: C, 53.5; H, 3.20; N, 8.90;Found: C, 53.3; H, 2.91; N, 8.91.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-methylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as yellow prisms (32% yield): mp 128-129° C.; ¹HNMR (CDCl₃) δ 7.86 (d, 1H), 7.79 (d, 1H), 7.55 (t, 1H), 7.28-7.39 (m,2H), 7.11 (t, 1H), 4.17 (s, 3H), 2.38 (s, 3H); EI/MS 402 m/e (M⁺);Calcd. for C₂₀H₁₄ClF₂N₃S: C, 59.8; H, 3.51; N, 10.5; Found: C, 59.6; H,3.44; N, 10.3.

3-(2-Chloro-6-fluorophenyl)-5-[5-(3-trifluoromethylphenylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow gum (66% yield): ¹H NMR (CDCl₃) δ 7.82(d, 1H), 7.88 (d, 2H), 7.82 (d, 2H), 7.78 (d, 1H), 7.53-7.58 (m, 2H),7.34-7.38 (m, 2H), 7.11 (t, 1H), 4.20 (s, 3H); EI/MS 437 m/e (M−1);Calcd. for C₂₀H₁₂ClF₄N₃S: C, 54.9; H, 2.76; N, 9.60; Found: C, 55.2; H,2.94; N, 9.60.

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (80% yield): mp 166° C.; ¹H NMR(CDCl₃) δ 7.88 (d, 1H), 7.78 (d, 1H), 7.75 (d, 2H), 7.66 (d, 2H),7.29-7.40 (m, 2H), 7.11 (t, 1H), 4.19 (s, 3H); EI/MS 437 m/c (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as yellowish crystals (56% yield): mp 113-114° C.;¹H NMR (CDCl₃) δ 7.66 (d, 1H), 7.65 (d, 1H), 7.56 (d, 2H), 7.29-7.39 (m,2H), 7.10 (t, 1H), 4.17 (s, 3H), 4.07 (q, 2H), 1.44 (t, 3H); EI/MS 413m/e (M−1); Calcd. for C₂₁H₁₇ClFN₃SO: C, 60.9; H, 4.14; N, 10.2; S, 7.75;Found: C, 60.7; H, 4.16; N, 9.93; S, 7.61.

3-(2,6-Difluorophenyl)-5-[5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (37% yield): mp 143-146° C.; ¹HNMR (CDCl₃) δ 7.88 (d, 1H), 7.77 (d, 1H), 7.75 (d, 2H), 7.66 (d, 2H),7.33-7.43 (m, 1H), 7.05 (t, 1H), 4.17 (s, 3H); EI/MS 421 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(2,3-dihydro-1-benzofuran-5-yl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellowish amorphous solid (21% yield): mp 180°C.; ¹H NMR (CDCl₃) δ 7.29-7.40 (m, 2H), 7.26 (s, 1H), 7.10-7.14 (m, 2H),6.89 (d, 1H), 4.04 (s, 3H), 3.93 (s, 3H), 3.92 (s, 3H); EI/MS 446 m/e(M⁺); Calcd. for C₂₁H₁₆Cl₂FN₃OS: C, 54.3; H, 3.47; N, 9.05; Found: C,54.1; H, 3.52; N, 8.76.

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (10% yield): mp 172° C.; ¹H NMR(CDCl₃) δ 7.45 (d, 2H), 7.29-7.39 (m, 2H), 7.23 (s, 1H), 7.11 (m, 1H),6.91 (d, 1H), 4.06 (q, 2H), 4.03 (s, 3H), 1.44 (t, 3H); EI/MS 448 m/e(M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white cubes (62% yield): mp 167-168° C.; ¹H NMR(CDCl₃) δ 7.67 (d, 2H), 7.65 (d, 2H), 7.42 (s, 1H), 7.29-7.39 (m, 2H),7.11 (m, 1H), 4.01 (s, 3H), 2.64 (s, 3H); EI/MS 452 m/e (M⁺); Calcd. forC₂₁H₁₄ClF₄N₃S: C, 55.8; H, 3.12; N, 9.30; Found: C, 55.9; H, 3.27; N,9.32.

3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white needles (75% yield): mp 184-185° C.; ¹HNMR (CDCl₃) δ 7.48 (d, 2H), 7.28-7.38 (m, 2H), 7.20 (s, 1H), 7.20 (s,1H), 7.10 (m, 1H), 6.91 (d, 2H), 4.06 (q, 2H), 4.00 (s, 3H), 2.60 (s,3H), 1.44 (t, 3H); EI/MS 428 m/e (M⁺); Calcd. for C₂₁H₁₄ClF₄N₃S: C,55.8; H, 3.12; N, 9.30; Found: C, 55.9; H, 3.27; N, 9.32.

3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(3-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as iridescent flakes (52% yield): mp 124-125° C.;¹H NMR (CDCl₃) δ 7.29-7.52 (m, 6H), 7.08-7.18 (m, 2H); EI/MS 468 m/e(M⁺); Calcd. for C₂₁H₁₄ClF₄N₃OS: C, 53.9; H, 3.02; N, 8.98; Found: C,53.8; H, 2.90; N, 8.87.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-methylphenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as iridescent plates (17% yield): mp 168-169° C.;¹H NMR (CDCl₃) δ 7.44-7.49 (m, 2H), 7.29-7.38 (m, 2H), 7.10 (m, 1H),6.97 (s, 1H), 6.96 (d, 1H), 4.01 (s, 3H), 2.64 (s, 3H), 2.37 (s, 3H);EI/MS 416 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[5-(3,4-dichlorophenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an amorphous white solid (28% yield): mp162-163° C.; ¹H NMR (CDCl₃) δ 7.65 (d, 1H), 7.45 (d, 1H), 7.29-7.40 (m,4H), 7.11 (m, 1H), 4.01(s, 3H), 2.62 (s, 3H); EI/MS 454 m/e (M+1);Calcd. for C₂₀H₁₃Cl₂FN₃S: C, 53.1; H, 2.81; N, 9.28; Found: C, 53.1; H,2.93; N, 9.12.

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-2-fluorophenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as iridescent plates (39% yield): mp 177-178° C.;¹H NMR (CDCl₃) δ 7.60 (dd, 1H), 7.40-7.45 (m, 1H), 7.27-7.38 (m, 3H),7.08-7.20 (m, 2H), 4.01 (s, 3H), 2.62 (s, 3H); EI/MS 436 m/e (M⁺);Calcd. for C₂₀H₁₃Cl₂F₂N₃S: C, 55.1; H, 3.00; N, 9.63; Found: C, 54.8; H,3.07; N, 9.46.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethylphenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as colorless needles (14% yield): mp 153-154° C.;¹H NMR (CDCl₃) δ 7.71 (t, 1H), 7.61 (s, 1H), 7.42-7.46 (m, H), 7.29-7.39(m, 2H), 7.11 (m, 1H), 4.02 (s, 3H), 2.66 (s, 3H); EI/MS 470 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-5-trifluoromethylphenyl)-2-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (27% yield): mp 141-142° C.; ¹HNMR (CDCl₃) δ 7.86 (dd, 1H), 7.58 (s, 1H), 7.56 (m, 1H), 7.28-7.39 (m,3H), 7.11 (m, 1H), 4.02 (s, 3H), 2.66 (s, 3H); EI/MS 470 m/e (M+2);Calcd. for C₂₁H₁₃ClF₅N₃S: C, 53.7; H, 2.79; N, 8.94; Found: C, 53.5; H,2.85; N, 8.94.

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an amorphous, white solid (14% yield): mp153-155° C.; ¹H NMR (CDCl₃) δ 7.44 (d, 2H), 7.29-7.39 (m, 2H), 7.22 (s,1H), 7.11 (t, 1H), 6.90 (d, 2H), 4.03-4.09 (m, 5H), 1.43 (t, 3H); EI/MS450 m/e (M+2); Calcd. for C₂₂H₁₉ClFN₃OS: C, 61.8; H, 4.48; N, 9.82;Found: C, 61.4; H, 4.42; N, 9.71.

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow gum (38% yield): ¹H NMR (CDCl₃) δ 7.71(d, 2H), 7.60 (d, 2H), 7.59 (s, 1H), 7.30-7.40 (m, 2H), 7.11 (t, 1H),4.04 (s, 3H), 2.36 (s, 3H); EI/MS 451 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chlorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a sticky, yellow foam (30% yield): ¹H NMR(CDCl₃) δ 7.54 (s, 1H), 7.38-7.41 (m, 4H), 7.29-7.35 (m, 2H), 7.11 (t,1H), 4.03 (s, 3H), 2.32 (s, 3H); EI/MS 417 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white needles (50% yield): mp 131-132° C.; ¹HNMR (CDCl₃) δ 7.47 (s, 1H), 7.38 (d, 4H), 7.29-7.36 (m, 2H), 7.11 (t,1H), 6.96 (d, 2H), 4.08 (q, 2H), 4.02 (s, 3H), 2.30 (s, 3H), 1.45 (t,3H); EI/MS 427 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-methoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow glass (30% yield): ¹H NMR (CDCl₃) δ7.48 (s, 1H), 7.41 (d, 2H), 7.29-7.38 (m, 2H), 7.11 (t, 1H), 6.98 (d,2H), 4.03 (s, 3H), 3.85 (s, 3H), 2.31 (s, 3H); EI/MS 413 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-methylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (39% yield): mp 158-159° C.;¹H NMR (CDCl₃) δ 7.50 (s, 1H), 7.29-7.39 (m, 4H), 7.27 (d, 2H), 7.11 (t,1H), 4.03 (s, 3H), 2.32 (s,3H); EI/MS 397 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(3-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellowish solid (16% yield): mp 133° C.; ¹HNMR (CDCl₃) δ 7.57 (s, 1H), 7.30-7.51 (m, 6H), 7.11 (t, 1H), 4.04 (s,3H), 2.34 (s,3H); EI/MS 467 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(3-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as free-flowing cubes (48% yield): mp 134-135° C.;¹H NMR (CDCl₃) δ 7.73 (br s, 1H), 7.55-7.67 (m, 4H), 7.29-7.39 (m, 2H),7.11 (t, 1H), 4.04 (s, 3H), 2.34 (s, 3H); EI/MS 451 m/e (M−1); Calcd.for C₂₁H₁₄ClF₄N₃S: C, 55.9; H, 3.13; N, 9.31; S, 7.09; Found: C, 55.8;H, 3.26; N, 9.26; S, 7.16.

3-(2-Chloro-6-fluorophenyl)-5-[5-(3-ethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (65% yield): mp 98-99° C.; ¹H NMR(CDCl₃) δ 7.51 (s, 1H), 7.26-7.39 (m, 3H), 7.00-7.14 (m, 2H), 6.92 (dd,1H), 4.07 (q, 2H), 4.02 (s, 3H), 2.34 (s, 3H), 1.43 (t, 3H); EI/MS 427m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-methylthiophenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white, fluffy solid (74% yield): mp 163-164°C.; ¹H NMR (CDCl₃) δ 7.51 (s, 1H), 7.40 (d, 2H), 7.29-7.37 (m, 4H), 7.11(t, 1H), 4.03 (s, 3H), 2.53 (s, 3H), 2.32 (s, 3H); EI/MS 429 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-phenoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow foam (51% yield): ¹H NMR (CDCl₃) δ 7.50(s, 1H), 7.29-7.45 (m, 6H), 7.04-7.17 (m, 6H), 4.03 (s, 3H), 2.33 (s,3H); EI/MS 475 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-isopropyl)phenylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as needles (15% yield): mp 143-144° C.; ¹H NMR(CDCl₃) δ 7.49 (s, 1H), 7.41 (d, 2H), 7.29-7.37 (m, 4H), 7.11 (m, 1H),4.03 (s, 3H), 2.96 (pentet, 1H), 2.33 (s, 3H), 1.29 (d, 6H); EI/MS 426m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-{5-[(3-fluorophenyl)-4-methyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as an amorphous white solid (89% yield): mp143-144° C.; ¹H NMR (CDCl₃) δ 7.55 (s, 1H), 7.04-7.44 (m, 7H), 4.02 (s,3H), 2.35 (s, 3H); EI/MS 402 m/e (M⁺); Calcd. for C₂₀H₁₄ClF₂N₃S: C,59.8; H, 3.5; N, 10.5; Found: C, 59.8; H, 3.56; N, 10.3.

3-(2-Chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (72% yield): mp 185-186° C.; ¹HNMR (CDCl₃) δ 7.49 (s, 1H), 7.44 (d, 2H), 7.29-7.38 (m, 2H), 7.09-7.18(m, 3H), 5.49 (m, 1H), 3.88-3.97 (m, 1H), 4.03 (s, 3H), 3.62-3.68 (m,1H), 2.35 (s, 3H), 1.98-2.07 (m, 1H), 1.87-1.91 (m, 2H), 1.601.73 (m,3H); EI/MS 484 m/e (M⁺); Calcd. for C₂₀H₁₄ClF₂N₃S: C, 59.8; H, 3.5; N,10.5; Found: C, 59.8; H, 3.56; N, 10.3.

3-(2-Chloro-6-fluorophenyl)-5-[5-(3,4-difluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white cubes (28% yield): mp 93° C.; ¹H NMR(CDCl₃) δ 7.54 (s, 1H), 7.28-7.37 (m, 3H), 7.19-7.25 (m, 2H), 7.11 (t,1H), 4.03 (s, 3H), 2.32 (s, 3H); EI/MS 419 (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(3-chloro-4-methylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white micro-needles (53% yield): mp 136-137° C.;¹H NMR (CDCl₃) δ 7.53 (s, 1H), 7.46 (s, 1H), 7.27-7.37 (m, 4H), 7.11 (t,1H), 4.02 (s, 3H), 2.42 (s, 3H), 2.32 (s, 3H); EI/MS 432 m/c (M⁺);Calcd. for C₂₁H₁₆Cl₂FN₃S: C, 58.3; H, 3.73; N, 9.7; S, 7.4; Found: C,58.0; H, 3.72; N, 9.43; S, 7.22.

3-(2-Chloro-6-fluorophenyl)-5-[5-(3-chloro-2-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellowish foam (15% yield): ¹H NMR (CDCl₃) δ7.78 (d, 1H), 7.65 (s, 1H), 7.58 (d, 1H), 7.45 (s, 1H), 7.29-7.39 (m,2H), 7.11 (t, 1H), 4.05 (s, 3H), 2.14 (s, 3H); EI/MS 485 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-3-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a colourless glass (8% yield): ¹H NMR (CDCl₃) δ7.79 (s, 1H), 7.58 (m, 1H), 7.29-7.39 (m, 2H), 7.11(t, 1H), 4.03 (s,3H), 2.33 (s, 3H); EI/MS 485 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow glass (39% yield): ¹H NMR (CDCl₃) δ7.68 (s, 1H), 7.46-7.54 (m, 3H), 7.29-7.39 (m, 2H), 7.11 (m, 1H), 4.04(s, 3H), 2.25 (s, 3H); EI/MS 470 (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-chloro-4-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an amorphous, yellowish solid (66% yield): mp65-66° C.; ¹H NMR (CDCl₃) δ 7.78 (s, 1H), 7.66 (s, 1H), 7.60 (d, 1H),7.52 (d, 1H), 7.29-7.39 (m, 2H), 7.11 (m, 1H), 4.05 (s, 3H), 2.17 (s,3H); EI/MS 486 m/e (M⁺); Calcd. for C₂₁H₁₃Cl₂F₄N₃S: C, 51.9; H, 2.69; N,8.64; Found: C, 51.6; H, 2.82; N, 8.45.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-4-trifluoromethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a colorless gum (33% yield): ¹H NMR (CDCl₃) δ7.64 (s, 1H), 7.29-7.46 (m, 3H), 7.08-7.14 (m, 3H), 4.04 (s, 3H), 2.23(d, 3H); EI/MS 485 m/e(M−1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-5-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a colorless glass (11% yield): ¹H NMR (CDCl₃) δ7.66-7.70 (m, 3H), 7.28-7.39 (m, 3H), 7.11 (m, 1H), 4.04 (s, 3H), 2.24(d, 3H); EI/MS 471 m/e (M+1).

3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(2-fluoro-4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was obtained as a yellow semi-solid (21% yield): ¹H NMR (CDCl₃)δ 7.43-7.53 (m, 3H), 7.29-7.39 (m, 2H), 7.11 (m, 1H), 3.90 (s, 3H), 2.44(s, 3H), 2.04 (d, 3H); EI/MS 484 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(4-trifluoromethylphenylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (5% yield): mp 146-147° C.; ¹H NMR(CDCl₃) δ 7.67 (d, 2H), 7.56 (d, 2H), 7.29-7.39 (m, 2H), 7.12 (m, 1H),3.90 (s, 3H), 2.43 (s, 3H), 2.16 (d, 3H); EI/MS 466 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white needles (41% yield): mp 148-149° C.; ¹HNMR (CDCl₃) δ 7.29-7.38 (m, 4H), 7.11 (m, 1H), 6.93 (d, 2H), 4.07 (q,2H), 3.88 (s, 3H), 2.39 (s, 3H), 2.11 (s, 3H), 1.44 (t, 3H); EI/MS 442m/e (M+); Calcd. for C₂₃H₂₁ClN₃OS: C, 62.4; H, 4.79; N, 9.51; Found: C,62.4; H, 4.87; N, 9.42.

3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(2-fluoro-4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was obtained as a white solid (64% yield): mp 112-116° C.; ¹HNMR (CDCl₃) δ 7.72 (t, J=4.3 Hz, 3H), 7.40-7.30 (m, 4H), 7.15-7.09 (m,1H), 4.09 (s, 3H); EI/MS 487 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃OS: C,49.20; H, 2.27; N, 8.61; Found: C, 48.95; H, 2.24; N, 8.48.

3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (66% yield): mp 88-92° C.; ¹H NMR(CDCl₃) δ 7.82 (d, J=8.0 Hz, 2H), 7.76 (s, 1H), 7.74 (d, J=8.0 Hz,2H),7.40-7.30 (m, 2H), 7.15-7.09 (m, 1H), 6.96-6.92 (m, 1H), 4.02 (m,3H). EI/MS 471 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃S: C, 50.86; H, 2.35;N, 8.90; Found: C, 50.81; H, 2.39; N, 8.77.

3-(2-Chloro-6-fluorophenyl)-5-[4-chloro-5-(4-ethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a light yellow solid (77% yield): mp 120-128°C.; ¹H NMR (CDCl₃) δ 7.63-7.58 (m, 3H), 7.39-7.29 (m, 2H), 7.14-7.08 (m,1H), 7.01-6.96 (m, 2H), 4.09 (q, J=6.9 Hz, 2H), 4.00 (s, 3H), 1.45 (t,J=6.9 Hz, 3H); EI/MS 447 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(11,2,2-tetrafluoroethoxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow gum (28% yield): ¹H NMR (CDCl₃) δ 7.55(s, 1H); 7.48 (d, 2H), 7.28-7.39 (m, 4H), 7.11 (m, 1H), 6.12, 5.94, 5.77(tt, J=53.2 Hz, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 500 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-fluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (31% yield): mp 112-113° C.; ¹HNMR (CDCl₃) δ 7.52 (s, 1H), 7.41-7.46 (m, 2H), 7.29-7.39 (m, 2H),7.08-7.17 (m, 3H), 4.03 (s, 3H), 2.31 (s, 3H); EI/MS 401 m/e (M−1);Calcd. for C₂₀H₁₄ClF₂N₃S: C, 59.8; H, 3.51; N, 10.5; Found: C, 59.6; H,3.66; N, 10.4.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2,4-difluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (44% yield): mp 112-113° C.; ¹HNMR (CDCl₃) δ 7.62 (s, 1H), 7.29-7.39 (m, 3H), 7.11 (s, 1H), 6.92-7.00(m, 2H), 4.04 (s, 3H), 2.21 (d, 3H); EI/MS 420 m/e (M⁺); Calcd. forC₂₀H₁₃ClF₃N₃S: C, 57.2; H, 3.12; N, 10.0; Found: C, 57.2; H, 3.21; N,9.95.

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-3-fluorolphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (47% yield): mp 132° C.; ¹H NMR(CDCl₃) δ 7.56 (s, 1H), 7.47 (t, 1H), 7.27-7.37 (m, 2H), 7.19-7.25 (m,2H), 7.11 (t, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 436 m/e (M⁺);Calcd. for C₂₀H₁₃Cl₂F₂N₃S: C, 55.1; H, 3.00; N, 9.63; Found: C, 55.3; H,3.10; N, 9.47.

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-chloro-2-fluorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow foam (24% yield): ¹H NMR (CDCl₃) δ 7.63(s, 1H), 7.29-7.39 (m, 3H), 7.21-7.24 (m, 2H), 7.11 (t, 1H), 4.03 (s,3H), 2.21 (d, 3H); EI/MS 436 m/e (M⁺); Calcd. for C₂₀H₁₃Cl₂F₂N₃S: C,55.1; H, 3.00; N, 9.63; Found: C, 55.0; H, 3.09; N, 9.47.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2-fluoro-3-trifluoromethylphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellowish solid (54% yield): mp 127-128° C.;¹H NMR (CDCl₃) δ 7.57-7.69 (m, 3H), 7.29-7.39 (m, 3H), 7.11 (t, 1H),4.04 (s, 3H), 2.23 (d, 3H); EI/MS 470 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[5-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (55% yield): mp 134-135° C.; ¹HNMR (CDCl₃) δ 7.47 (s, 1H), 7.28-7.38 (m, 2H), 7.10 (t, 1H), 6.99-6.96(d, 1H), 6.94 (ds, 2H), 4.30 (s, 4H), 4.02 (s, 3H), 2.31 (s, 3H); EI/MS442 m/c (M⁺); Calcd. for C₂₂H₁₇ClFN₃O₂S: C, 59.8; H, 3.88; N, 9.51;Found: C, 59.7; H, 4.06; N, 9.45.

3-(2-Chloro-6-fluorophenyl)-5-[5-(1,3-benzodioxin-5-yl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white crystals (61% yield): mp 122-123° C.; ¹HNMR (CDCl₃) δ 7.47 (s, 1H), 7.28-7.38 (m, 2H), 7.10 (d, 2H), 6.92-6.96(m, 2H), 6.87 (d, 2H), 6.01 (d, 2H), 4.02 (s, 3H), 2.30 (s, 3H); EI/MS428 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-methoxyethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a pale yellow glass (32% yield): ¹H NMR (CDCl₃)δ 7.48 (s, 1H), 7.39 (d, 2H), 7.29-7.38 (m, 2H), 7.11 (t, 1H), 7.00 (d,2H), 4.17 (m, 2H), 4.02 (s, 3H), 3.79 (m, 2H), 3.47 (s, 3H), 2.30 (s,3H); EI/MS 457 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-methylpropenyloxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a pale liquid (11% yield): ¹H NMR (CDCl₃) δ 7.48(s, 1H), 7.39 (d, 2H), 7.28-7.37 (m, 2H), 7.10 (t, 1H), 6.98 (d, 2H),6.01-6.14 (m, 1H), 5.44 (d, 1H), 5.31 (d, 1H), 4.58 (d, 2H), 4.02 (s,3H), 2.34 (s, 3H); EI/MS 439 m/e (M−CH₃)

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(1-methylethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-2,4-triazole

Product was isolated as a hard, yellowish glass (40% yield): ¹H NMR(CDCl₃) δ 7.52 (s, 1H), 7.29-7.39 (m, 3H), 7.11 (t, 1H), 6.99-7.05 (m,2H), 6.89 (d, 1H), 4.59 (pentet, 1H), 4.03 (s, 3H), 2.35 (s, 3H), 1.36(d, 6H); EI/MS 441 m/e (M−1); Calcd. for C₂₃H₂₁ClFN₃OS: C, 62.5; H,4.79; N, 9.51; Found: C, 62.7; H, 4.79; N, 9.50.

3-(2-Chloro-6-fluorophenyl)-5-[5-(2,4-dichlorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white crystals (4% yield): mp 114-115° C.; ¹HNMR (CDCl₃) δ 7.62 (s, 1H), 7.53 (s, 1H), 7.29-7.39 (m, 4H), 7.11 (t,1H), 4.04 (s, 3H), 2.14 (s, 3H); EI/MS 453 m/e (M⁺); Calcd. forC₂₀H₁₃Cl₃FN₃S: C, 53.1; H, 2.89; N, 9.28; Found: C, 52.9; H, 3.30; N,8.86.

3-(2-Chloro-6-fluorophenyl)-5-[5-(3,4-dichlorophenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (48% yield): mp 138° C.; ¹H NMR(CDCl₃) δ 7.54 (d, 2H), 7.51 (s, 1H), 7.29-7.39 (m, 4H), 7.11 (t, 1H),4.03 (s, 3H), 2.33 (s, 3H); EI/MS 452 m/e (M−1); Calcd. forC₂₀H₁₃Cl₃FN₃S: C, 53.1; H, 2.89; N, 9.28; Found: C, 53.1; H, 3.05; N,9.24.

3-(2-chloro-6-fluorophenyl)-5-[3-methyl-5-(4-trifluoromethoxyphenyl)-thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a tan solid (72% yield): mp 96-97° C.; ¹H NMR(CDCl₃) δ 2.41 (s, 3H), 4.05 (s, 3H), 7.07 (m, 1H), 7.21-7.38 (m, 5H),7.62 (d, 2H); EI/MS 467 m/e (M+).

3-(2-Chloro-6-fluorophenyl)-5-{3-methyl-5-[4-(trifluoromethyl)phenyl]-thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (70% yield): mp 85-86° C.; ¹HNMR (CDCl₃) δ 2.43 (s, 3H), 4.12 (s, 3H), 7.10 (m, 1H), 7.25-7.41 (m,3H), 7.72 (q, 4H, J=8.3 Hz); EI/MS 451 m/e (M+).

3-(2-Chloro-6-fluorophenyl)-5-[3-methyl-5-(3-chloro-4-fluorophenyl)-thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a tan solid (58% yield): mp 121-122° C.; ¹H NMR(CDCl₃) δ 2.25 (s, 3H), 3.95 (s, 3H), 6.95-7.22 (m, 5H), 7.31 (m, 1H),7.55 (d, 2H); EI/MS 436 m/e (M+).

3-(2,6-difluorophenyl)-5-{3-chloro-5-[4-(trifluoromethoxy)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a yellow solid (65% yield): mp 105-107° C.; ¹HNMR (CDCl₃) δ 7.63-7.59 (m, 2H), 7.41-7.36 (m, 1H), 7.30-7.25 (m, 3H),7.06-7.00 (m, 2H), 4.07 (s, 3H); EI/MS 471 m/e (M+); Calcd forC₂₀H₁₁ClF₅N₃OS: C, 50.91; H, 2.35; N, 8.91; S, 6.80; Found: C, 50.90; H,2.44; N, 8.64; S, 6.93.

3-(2,6-Difluorophenyl)-5-[3-chloro-5-(4-methylphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white foamy solid (69% yield): mp139-141° C.; ¹H NMR (CDCl₃) δ 7.47 (m, 2H), 7.41-7.35 (m, 1H), 7.26-7.22(m, 3H), 7.05-7.02 (m, 2H), 4.07 (s, 3H), 2.39 (s, 3H); EI/MS 401 m/e(M+); Calcd for C₂₀H₁₄ClF₂N₃S: C, 59.78; H, 3.51; N, 10.46; S, 7.98;Found: C, 59.83; H, 3.61; N, 10.22; S, 8.16.

3-(2,6-Difluorophenyl)-5-[3-chloro-5-(4-ethoxyphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a light yellow solid (64% yield): mp 120-123°C.; ¹H NMR (CDCl₃) δ 7.50 (d, 2H, J=8.7 Hz), 7.38 (m, 1H), 7.15 (s, 1H),7.05-6.99 (m, 2H), 6.94 (d, 2H, J=8.7 Hz), 4.06 (m, 5H), 1.44 (t, 3H,J=6.9 Hz); EI/MS 432 m/e (M+H); Calcd for C₂₁H₁₆ClF₂N₃OS: C, 58.40; H,3.73; N, 9.73; S, 7.42; Found: C, 58.44; H, 3.88; N, 9.48; S, 7.23.

3-(2,6-Difluorophenyl)-5-{3-chloro-5-[4-trifluoromethyl)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (63% yield): mp 156-162° C.; ¹HNMR (CDCl₃) δ 7.70 (s, 4H), 7.42-7.35 (m, 2H), 7.03 (t, 2H, J=8.05 Hz),4.08 (s, 3H); EI/MS 455 m/e (M+); Calcd for C₂₀H₁₁ClF₅N₃S: C, 52.70; H,2.43; N, 9.22; S, 7.03; Found: C, 52.81; H, 2.50; N, 9.13; S, 7.11.

3-(2-Chloro-6-fluorophenyl)-5-{3-chloro-5-[4-trifluoromethoxy)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (62% yield): mp 120-123° C.;¹H NMR (CDCl₃) δ 7.62 (ddd, 2H, J=2.1, 2.9, 8.7 Hz), 7.40-7.26 (m, 5H),7.15-7.08 (m, 1H), 4.08 (s, 3H); EI/MS 487 m/e (M+); Calcd forC₂₀H₁₁Cl₂F₄N₃OS: C, 49.20; H. 2.27; N, 8.61; S, 6.57; Found: C, 49.42;H, 2.38; N, 8.37; S, 6.61.

3-(2-Chloro-6-fluorophenyl)-5-{3-chloro-5-[4-(trifluoromethyl)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (60% yield): mp 133-136° C.;¹H NMR (CDCl₃) δ 7.70 (s, 4H), 7.38-7.30 (m, 3H), 7.15-7.09 (m, 1H),4.09 (s, 3H); EI/MS 471 m/e (M+); Calcd for C₂₀H₁₁Cl₂F₄N₃S: C, 50.86; H,2.35; N, 8.90; S, 6.79; Found: C, 51.01; H, 2.36; N, 8.67; S, 6.48.

3-(2-Chloro-6-fluorophenyl)-5-[3-chloro-5-(4-methylphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a light yellow solid (69% yield): mp 111-115°C.; ¹H NMR (MHz, CDCl₃) δ 7.49 (d, 2H, J=8.0 Hz), 7.46-7.23 (m, 5H),7.14-7.08 (m, 1H), 4.09 (s, 3H); EI/MS 417 m/e (M+); Calcd forC₂₀H₁₄Cl₂FN₃S: C, 57.43; H, 3.37; N, 10.04; S, 7.66; Found: C, 57.19; H,3.46; N, 9.64; S, 7.16.

3-(2-Chloro-6-fluorophenyl)-5-[3-chloro-5-(4-ethoxyphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (66% yield): mp 126-128° C.;¹H NMR (CDCl₃) δ 7.50 (dd, 2H, J=8.7, 2.0 Hz), 7.39-7.29 (m, 2H), 7.15(s, 1H), 7.14-7.08 (m, 1H), 6.96-6.92 (m, 1H), 4.11 (m, 5H), 1.44 (t,3H, J=7.1 Hz); EI/MS 419 m/e (M−Et); Calcd for C₂₁H₁₆Cl₂FN₃OS: C, 56.26;H, 3.60; N, 9.37; S, 7.15; Found: C, 56.33; H, 3.62; N, 9.31; S, 7.13.

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-bromophenyl)-3-chlorothien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (44% yield): mp 126-128° C.;¹H NMR (CDCl₃) δ 7.57 (d, 2H, J=8.4 Hz), 7.46 (d, 2H, J=8.4 Hz),7.37-7.29 (m, 2H), 7.26 (s, 1H and CDCl₃), 7.14-7.08 (m, 1H), 4.08 (s,3H); EI/MS 483 m/e (M+); Calcd for C₁₉H₁₁BrCl₂FN₃S: C, 47.23; H, 2.29;N, 8.70; S, 6.64; Found: C, 47.32; H, 2.34; N, 8.46; S, 6.68.

3-(2-Chloro-6-fluorophenyl)-5-{3-chloro-5-[4-(methylthio)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a light yellow solid (66% yield): mp 125-126°C.; ¹H NMR (CDCl₃) δ 7.50 (d, 2H, J=8.7 Hz), 7.40-7.23 (m, 5H),7.14-7.08 (m, 1H), 4.08 (s, 3H), 2.52 (s, 3H); EI/MS 449 m/e (M+); Calcdfor C₂₀H₁₄Cl₂FN₃S₂: C, 53.34; H, 3.13; N, 9.33; S, 14.24; Found: C,53.17; H, 3.19; N, 9.19; S, 14.28.

3-(2-Chloro-6-fluorophenyl)-5-{4-bromo-3-chloro-5-[4-(trifluoromethoxy)phenyl]thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (18%): mp 170-172° C.; ¹H NMR(CDCl₃) δ 7.69 (d, 2H, J=8.7 Hz), 7.38-7.29 (m, 4H), 7.23-7.09 (m, 1H),4.09 (s, 3H); EI/MS 567 m/e (M+).

3-(2-Chloro-6-fluorophenyl)-5-{4-bromo-3-chloro-5-[4-(trifluoromethyl)phenyl]-thien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (28% yield): mp 167-170° C.; ¹HNMR (CDCl₃) δ 7.50 (dd, 2H, J=8.7, 2.0 Hz), 7.39-7.29 (m, 2H), 7.15 (s,1H), 7.14-7.08 (m, 1H), 6.96-6.92 (m, 1H), 4.11 (m, 5H), 1.44 (t, 3H,J=7.1 Hz); EI/MS 551 m/e (M+).

3-(2-Chloro-6-fluorophenyl)-5-[4-bromo-3-chloro-5-(4-ethoxyphenyl)thien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (41% yield): mp 145-150° C.; ¹HNMR (CDCl₃) δ 7.58 (d, 2H, J=8.7 Hz), 7.40-7.30 (m, 2H), 7.14-7.08 (m,1H), 6.99 (d, 2H, J=8.7 Hz), 4.13-4.03 (m, 5H), 1.45 (t, 3H, J=6.9 Hz);EI/MS m/e 527 (M+).

3-(2-Chloro-6-fluorophenyl)-5-[4-(4-trifluoromethoxyphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (69% yield): mp 108-109° C.;¹H NMR (CDCl₃) δ 2.16 (s, 3H), 3.92 (s, 3H), 6.96 (m, 1H), 7.11-7.29 (m,7H); EI/MS 467 m/e (M⁺)

3-(2-Chloro-6-fluorophenyl)-5-[4-(4-ethoxyphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an off-white solid (80% yield): mp 124-127° C.;¹H NMR (CDCl₃) δ 1.45 (t, 3H, J=7.0 Hz), 2.31 (s, 3H), 4.06 (s, 3H),6.96 (d, 2H, J=8.4 Hz), 6.98-7.13 (m, 1H), 7.30-7.39 (m, 5H); EI/MS 427m/e (M+H); Calcd. for C₂₂H₁₉ClFN₃OS: C, 61.75; H, 4.48; N, 9.82; Found:C, 61.74; H. 4.53; N, 9.63.

3-(2-Chloro-6-fluorophenyl)-5-[4-(4-trifluoromethylphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (66% yield): mp 102-103° C.; ¹HNMR (CDCl₃) δ 2.34 (s, 3H), 4.08 (s, 3H), 7.10 (dd, 1H, J=7.3 Hz),7.31-7.38 (m, 2H), 7.49 (s, 1H), 7.53 (d, 2H, J=8.0 Hz), 7.71 (d, 2H,J=8.0 Hz); EI/MS 467 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[4-(4-isopropylphenyl)-3-methylthien-2-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (53% yield): mp 109-111° C.; ¹HNMR (CDCl₃) δ 1.30 (d, 6H, J=6.6 Hz), 2.33 (s, 3H), 2.96 (m, 1H), 4.06(s, 3H), 7.08-7.14 (m, 1H), 7.28-7.38 (m, 7H); EI/MS 425 m/e (M+H);Calcd. for C₂₃H₂₃ClFN₃S: C, 64.86; H, 4.97; N, 9.86; Found: C, 64.51; H,5.02; N, 9.78.

3-(2-Methylphenyl)-5-{4-methyl-5-[4-trifluoromethoxyphenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was obtained as a yellowish solid (83% yield): mp 122-123° C.;¹H NMR (CDCl₃) δ 7.98-8.01 (m, 1H), 7.48-7.52 (m, 3H), 7.27-7.32 (m,5H), 3.98 (s, 3H), 2.69 (s, 3H), 2.33 (s, 3H); EI/MS 430 m/e (M+1).

3-(2-Methylphenyl)-5-{4-methyl-5-[4-trifluoromethylphenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was obtained as a yellow solid (68% yield): mp 149-150° C.; ¹HNMR (CDCl₃) δ 7.98-8.00 (m, 1H), 7.71 (d, J=8.1 Hz, 2H), 7.61 (d, J=8.4Hz, 2H), 7.56 (s, 1H), 7.27-7.30 (m, 3H), 3.99 (s, 3H), 2.69 (s, 3H),2.36 (s, 3H); EI/MS 414 m/e(M+1).

3-(2-Methylphenyl)-5-[5-(4-ethoxyphenyl)-4-methylthien-3-yl]-methyl-1H-1,2,4-triazole

Product was obtained as white needles (11% yield): mp 160-161° C.; ¹HNMR (CDCl₃) δ 7.98-8.01 (m, 1H), 7.44 (s, 1H), 7.29-7.43 (m, 2H),7.26-7.29 (m, 3H), 6.94-6.99 (m, 2H), 4.08 (q, J=6.9 Hz, 2H), 3.98 (s,3H), 2.69 (s, 3H), 2.31 (s, 3H), 1.45 (t, J=7.2 Hz, 3H); EI/MS 390 m/e(M+1).

Example 2

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(3-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

A solution of3-(2-chloro-6-fluorophenyl)-1-methyl-5-[5-(3-trifluoromethylphenyl)thien-3-yl]-1H-1,2,4-triazole(0.45 g, 1 mmol) and N-chlorosuccinimide (0.15 g, 1.1 mmol) in methylenechloride/glacial acetic acid (1:1, 2 mL) was refluxed under nitrogen for2 days, cooled to room temperature, poured into water (10 mL) andextracted with ether (3×20 mL). The combined ethereal extracts werewashed with water (3×30 mL), saturated aqueous sodium bicarbonate (50mL) and brine (30 mL), dried over magnesium sulphate and chromatographedon silica to afford the product as a white solid (0.37 g, 76%): mp53-54° C.; ¹H NMR (CDCl₃) δ 7.79 (s, 1H), 7.71 (d, 2H), 7.60 (d, 1H),7.54 (t, 1H), 7.44 (s, 1H), 7.30-7.40 (m, 2H), 7.11 (t, 1H), 4.05 (s,3H); EI/MS 472 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃S: C, 50.9; H, 2.35; N,8.90; Found: C, 50.9; H, 2.49; N, 8.82.

The following compounds were prepared according to the general procedureof Example 2.

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(3-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (96% yield): mp 98-99° C.; ¹H NMR(CDCl₃) δ 7.29-7.46 (m, 6H), 7.21 (br, 1H), 7.11 (t, 1H), 4.04 (s, 3H);EI/MS 488 m/e (M⁺); Calcd. for C₂₀H₁₁Cl₂F₄N₃OS: C, 49.2; H, 2.27; N,8.61; Found: C, 49.4; H, 2.40; N, 8.49.

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(2-fluoro-4-trifluoromethylphenylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (66% yield): mp 157-158° C.; ¹HNMR (CDCl₃) δ 7.72 (t, 1H), 7.62 (s, 1H), 7.44-7.49 (m, 2H), 7.33-7.38(m, 2H), 7.12 (t, 1H), 4.04 (s, 3H); EI/MS 490 m/e (M⁺); Calcd. forC₂₀H₁₀Cl₂F₅N₃S: C, 49.0; H, 2.06; N, 8.57; Found: C, 48.5; H, 2.29; N,8.34.

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-chloro-2-fluorophenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white, iridescent flakes (57% yield): mp197-198° C.; ¹H NMR (CDCl₃) δ 7.49-7.54 (m, 2H), 7.29-7.38 (m, 2H),7.18-7.24 (m, 2H), 7.11 (t, 1H), 4.04 (s, 3H); EI/MS 458 m/e (M+1);Calcd. for C₁₉H₁₀Cl₃F₂N₃S; C, 50.0; H, 2.21; N, 9.20; Found: C, 49.6; H,2.31; N, 8.94.

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-trifluoromethylphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as an amorphous white solid (64% yield): mp145-146° C.; ¹H NMR (CDCl₃) δ 7.66 (dd, 4H), 7.46 (s, 1H), 7.30-7.40 (m,2H), 7.12 (m, 1H), 4.05 (s, 3H); EI/MS 472 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as needles (12% yield): mp 154-155° C.; ¹H NMR(CDCl₃) δ 7.56 (d, 2H), 7.30-7.40 (m, 2H), 7.25-7.28 (m, 3H), 7.11 (m,1H), 4.04 (s, 3H); EI/MS 488 m/e (M⁺).

Example 3

3-(2-Chloro-6-fluorophenyl)-5-[2-bromo-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

A solution of3-(2-chloro-6-fluorophenyl)-1-methyl-5-[5-(4-trifluoromethoxyphenyl)thien-3-yl]-1H-1,2,4-triazole (0.26 g, 0.6 mmol) in glacial acetic acid (7mL) was cooled to 6° C. Bromine (0.1 g, 32 μL, 0.6 mmol) was added tothe reaction and allowed to warm to room temperature and stirred for 16hours. The reaction mixture was poured into water (50 mL) and extractedwith ether (3×30 mL). The combined ethereal extracts were washed withwater (100 mL), saturated aqueous sodium bicarbonate (100 mL), aqueoussodium bisulphite (10% solution, 50 mL) and brine (70 mL), dried overmagnesium sulphate and concentrated. Column chromatography gave theproduct (297 mg, 97%) as a yellowish solid: mp 135-136° C.; ¹H NMR(CDCl₃) δ 7.57 (d, 1H), 7.25-7.40 (m, 5H), 7.12 (t, 1H), 4.04 (s, 3H);EI/MS 533 m/c (M⁺).

The following compounds were prepared according to the general procedureof Example 3.

3-(2-Chloro-6-fluorophenyl)-5-[2-bromo-4-methyl-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a clear, thick gum (99% yield): ¹H NMR (CDCl₃) δ7.42 (d, 2H), 7.27-7.31 (m, 4H), 7.10 (t, 1H), 3.97 (s, 3H), 2.18 (s,3H); EI/MS 547 m/e (M⁺).

Example 4

3-(2-Chloro-6-fluorophenyl)-5-[2-methyl-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

n-Butyllithium (2.5 N in hexanes, 0.25 mL, 0.4 mmol) was added to asolution of3-(2-chloro-6-fluorophenyl)-5-[2-bromo-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole(190 mg, 0.3 mmol) in dry THF (2 mL) at −75° C. and stirred for 1 hour.Iodomethane (66 mg, 29 μL, 0.5 mmol) was added to this reaction mixtureand stirred at −75° C. for 30 minutes. After warming to 0° C., saturatedaqueous ammonium chloride (2 mL) was added, followed by water (30 mL)and the mixture was extracted with ether (3×10 mL). The combinedethereal extracts were washed with water (30 mL) and brine (10 mL),dried over magnesium sulphate and chromatographed on silica to give theproduct (49 mg, 29%) as a yellow solid: mp 153-155° C.; ¹H NMR (CDCl₃) δ7.59 (d, 2H), 7.29-7.39 (m, 3H), 7.25 (d, 2H), 7.12 (t, 1H), 4.01 (s,3H), 2.62 (s, 3H); EI/MS 467 m/e (M−1).

The following compounds were prepared according to the general procedureof Example 4.

3-(2-Chloro-6-fluorophenyl)-5-[2,4-dimethyl-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a hard, colourless glass (59% yield): ¹H NMR(CDCl₃) δ 7.45-7.47 (d, 2H), 7.28-7.40 (m, 4H), 7.12 (t, 1H), 3.98 (s,3H), 2.41 (s, 3H), 2.13 (s, 3H); EI/MS 481 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-[2-chloro-4-methyl-5-(4-trifluoromethoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as a colourless gum (65% yield): ¹H NMR (CDCl₃) δ7.45 (d, 2H), 7.28-7.38 (m, 4H), 7.12 (t, 1H), 3.98 (s, 3H), 2.18 (s,3H); EI/MS 501 m/e (M−1).

Example 5

3-(2-Chloro-6-fluorophenyl)-5-[(5-(4-fluoromethylthio)phenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

A solution of 3-(2-chloro-6-fluorophenyl)-5-[4-methyl-5-(4-methlsulfinylphenyl)-thien-3-yl]-1-methyl-1H-1,2,4-triazole (160 mg, 0.36 mmol) inchloroform (4 mL) was treated with (diethylamino)sulphur trifluoride (77mg, 0.5 mmol) and antimony trifluoride (1.1 mg, 4.8 mmol). Suspendedsolids gradually dissolved upon stirring at room temperature. Saturatedaqueous sodium bicarbonate (3 mL) and 50% aqueous sodium hydroxide (1drop via Pasteur pipette) were added after 5 hours stirring at roomtemperature. The organic phase was collected and the aqueous phase wasextracted with chloroform (2×10 mL). The combined organic extracts werewashed with water (10 mL), saturated sodium bicarbonate (10 mL) andbrine (10 mL), dried over magnesium sulphate and chromatographed onsilica gel to furnish the target compound (22 mg, 37%): ¹H NMR (CDCl₃) δ7.55-7.58 (m, 3H), 7.46 (d, 2H), 7.29-7.39 (m, 2H), 7.11 (t, 1H), 5.86(s, 1H), 5.69 (s, 1H), 4.03 (s, 3H), 2.34 (s, 3H); EI/MS 447 m/e (M+1).

Example K

4-{4-Chloro-5-[3-(2-chloro-6-fluorolphenyl)-1-methyl-1H-1,2,4-triazol-5-yl]thien-2-yl}phenol

5-[3-Chloro-5-(4-ethoxyphenyl)thien-2-yl]-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole(542 mg, 1.20 mmol) was dissolved in CH₂Cl₂ (12 mL) under N₂ and wascooled to 0° C. To this was added BBr₃ (1.0 M solution in CH₂Cl₂; 2.0mL, 2.0 mmol) dropwise via syringe. The cooling bath was removedimmediately and the reaction mixture was allowed to warm to 25° C. andstirred for 20 hours. The mixture was poured onto H₂O (100 mL) andstirred at 25° C. for 30 min. The layers were partitioned, and theaqueous layer was extracted with CH₂Cl₂ (2×50 mL). The combined organicextracts were washed with H₂O (50 mL) and satd aq NaCl (50 mL), dried(Na₂SO₄), filtered and concentrated. Column chromatography (10-80%Et₂O-hexanes) gave the product (414 mg, 81%) as a light yellow solid: mp205-209° C.; ¹H NMR (CDCl₃) δ 7.38 (m, 2H), 7.34-7.25 (m, 2H), 7.09-7.03(m, 2H), 6.80 (m, 2H), 4.00 (s, 3H); EI/MS 420 m/e (M+).

The following compounds were prepared according to the general procedureof Example K.

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Product was isolated as white plates (42% yield): mp 221-222° C.; ¹H NMR(CDCl₃) δ 7.47 (s, 1H), 7.26-7.37 (m, 4H), 7.11 (t, 1H), 6.84 (d, 2H),5.77 (br, 1H), 4.02 (s, 3H), 2.25 (s, 3H); EI/MS 399 m/e (M−1).

4-{3-Chloro-4-[3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazol-5-yl]thien-2-yl}phenol

Product was isolated as a salmon-colored solid (27% yield): mp 239-242°C.; ¹H NMR (CDCl₃) δ 7.59 (s, 1H), 7.49 (d, 2H, J=8.05 Hz), 7.35-7.28(m, 2H), 7.15-7.10 (m, 1H), 6.85 (d, 2H, J=8.42), 6.31 (bs, 1H), 4.00(s, 3H); EI/MS 420 m/e (M+H), 418 ml/e (M−H).

4-{5-[3-(2-Chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazol-5-yl]-4-methylthien -3-yl}phenol

Product was isolated as an off-white solid (50% yield): mp 233-235° C.;¹H NMR (CDCl₃) δ 2.29 (s, 3H), 4.06 (s, 3H), 5.03 (s, 1H), 6.88 (d, 2H,J=8.4 Hz), 7.08-7.13 (m, 1H), 7.24-7.27 (m, 3H), 7.30-7.36 (m, 2H);EI/MS 399 m/e (M−H); Calcd. for C₂₀H₁₅ClFN₃OS: C, 60.07; H, 3.78; N,10.51; Found: C, 60.06; H, 3.88; N, 10.28.

Example L

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

Dilute hydrochloric acid (4 N, 2.5 mL) was added to a suspension of3-(2-chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole(0.62 g, 1.3 mmol) in tetrahydrofuran (2.5 mL), stirred at roomtemperature for 30 minutes, poured into water (20 mL) and extracted withether (3×20 mL). The combined ethereal extracts were washed with water(100 mL) and brine (50 mL), dried over magnesium sulphate andconcentrated under reduced pressure to leave the desired product (0.49g, 96%) as a white solid. ¹H NMR (CDCl₃) and mass spectrometry dataindicated this material to be free of impurities and to be comparable toauthentic material prepared according to that in Example K.

Example 6

3-(2-Chloro-6-fluorophenyl)-5-[4-methyl-5-(4-n-propoxyphenyl)thien-3-yl]-1-methyl-1H-1,2,4-triazole

A solution of3-(2-chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole (97 mg, 0.2 mmol) in dry THF (2 mL)was cooled to −3° C. and treated with sodium hydride (95% suspension inmineral oil, 9 mg, 0.4 mmol). After stirring for 5 minutes, iodopropane(62 mg, 0.4 mmol) was added and the reaction was allowed to stir at roomtemperature for 16 hours. An additional batch of sodium hydride (9 mg,0.4 mmol) and iodopropane (62 mg, 0.4 mmol) was added and the reactionheated to 45° C. After dilution with water (5 mL), the product wasextracted with ether (3×5 mL). The combined ethereal extracts werewashed with water (2×5 mL) and brine (10 mL), dried over magnesiumsulphate and concentrated. Column chromatography gave the product (101mg, 93%) as a colorless glass: ¹H NMR (CDCl₃) δ 7.49 (s, 1H), 7.27-7.41(m, 4H), 7.12 (t, 1H), 6.98 (d, 2H), 4.04 (s, 3H), 3.99 (t, 2H), 2.32(s, 3H), 1.85 (m, 2H), 1.08 (t, 3H); EI/MS 441 m/e (M+1).

The following compounds were prepared according to the general procedureof Example 6.

3-(2-Chloro-6-fluorophenyl)-5-{4-methyl-5-[4-(2,2,2-trifluoroethoxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as white plates (15% yield): mp 161-162° C.; ¹H NMR(CDCl₃) δ 7.62 (s, 1H), 7.57 (d, 2H), 7.32-7.39 (m, 2H), 7.11 (t, 1H),7.03 (d, 2H), 4.42 (q, 2H), 4.03 (s, 3H), 2.31 (s, 3H); EI/MS 481 m/e(M+1).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-fluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as colourless cubes (43% yield): mp 121-122° C.; ¹HNMR (CDCl₃) δ 7.49 (s, 1H), 7.41(d, 2H), 7.29-7.39 (m, 2H), 7.11 (t,1H), 7.00 (d, 2H), 4.87 (t, 1H), 4.71 (t, 1H), 4.31 (t, 1H), 4.22 (s,3H), 4.03 (s, 3H), 2.31 (s,3H); EI/MS 445 m/e (M+1).

Example 7

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

A solution of3-(2-chloro-6-fluorophenyl)-5-[5-(4-hydroxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole (300 mg, 0.7 mmol) in dry DMF (3 mL)was treated with aqueous sodium hydroxide (25% solution, 120 μL, 3.5mmol) at a dropwise rate. After stirring at room temperature for 30minutes, hexafluoropropene was bubbled in for 35 minutes and thenstirred at room temperature for 40 minutes. The reactants were pouredinto water (50 mL) and extracted with ether (3×40 mL). The combinedethereal extracts were washed with water (4×150 mL) until the aqueouswashings were neutral and then with brine (100 mL), dried over magnesiumsulphate, and concentrated. Column chromatography afforded a colourlessgum (0.24 g, 58%): ¹H NMR (CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H),7.26-7.39 (m, 4H), 7.11 (t, 1H), 5.10 & 4.95 (d sextets, 1H), 4.03 (s,3H), 2.33 (s,3H); EI/MS 549 (M+1).

The following compounds were prepared according to the general procedureof Example 7.

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2,2-dichloro-1,1-difluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

The product was isolated as a pale, yellow foam (58% yield): ¹H NMR(CDCl₃) δ 7.54 (s, 1H), 7.48 (d, 2H), 7.29-7.39 (m, 4H), 7.11 (t, 1H),5.95 (t, 1H), 4.03 (s, 3H), 2.33 (s,3H); EI/MS 533 m/e (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

The product was isolated as a colourless glass (78% yield): ¹H NMR(CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H), 7.29-7.39 (m, 4H), 7.11 (t, 1H),6.38 & 6.22 (t, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 515 m/e (M−1);Calcd. for C₂₂H₁₅Cl₂F₄N₃O₂s: C, 51.3; H. 2.94; N, 8.16; S, 6.21; Found:C, 51.2; H, 3.01; N, 8.07; S, 6.21.

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-4-methylthien-3-yl}-1-methyl-1H-1,2,4-triazole

The product was isolated as a white solid (76% yield): mp 80-82° C.; ¹HNMR (CDCl₃) δ 7.55 (s, 1H), 7.49 (d, 2H), 7.29-7.39 (m, 4H), 7.11 (t,1H), 6.64 & 6.48 (t, 1H), 4.03 (s, 3H), 2.33 (s, 3H); EI/MS 562 m/e(M+1).

3-(2-Chloro-6-fluorophenyl)-5-[5-(4-difluoromethoxyphenyl)-4-methylthien-3-yl]-1-methyl-1H-1,2,4-triazole

The product was isolated as an amorphous white solid (52% yield): mp115-116° C.; ¹H NMR (CDCl₃) δ 7.53 (s, 1H), 7.47 (d, 2H), 7.29-7.45 (m,2H), 7.20 (d, 2H), 7.11 (t, 1H), 6.57 (t, J=73.8 Hz, 1H), 4.03 (s, 3H),2.32 (s, 3H); EI/MS 450 (M⁺).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

The product was isolated as a white solid (65% yield): mp 115-116° C.;¹H NMR (CDCl₃) δ 7.55 (d, 2H), 7.11-7.31 (m, 5H), 7.02 (t, 1H), 6.13 &6.30 (t, 1H), 3.99 (s, 3H), 2.34 (s, 3H); EI/MS 515 m/e (M−1).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2,2-dichloro-1,1-difluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (72% yield): mp 119-120° C.; ¹HNMR (CDCl₃) δ 7.55 (d, 2H), 7.21-7.31 (m, 3H), 7.15 (s, 1H), 7.02 (t,1H), 5.85 (t, 1H), 3.99 (s, 3H), 2.34 (s, 3H); EI/MS 534 m/c (M+1).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a clear thick oil (58% yield): ¹H NMR (CDCl₃) δ7.48 (d, 2H), 7.15-7.22 (m, 3H), 7.11 (s, 1H), 6.99 (t, 1H), 4.79-4.95(m, 1H), 3.93 (s, 3H), 2.27 (s, 3H); EI/MS 550 m/e (M+1).

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-chlorothien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white crystalline solid (68% yield): mp137-140° C.; ¹H NMR (CDCl₃) δ 7.60 (m, 2H), 7.40-7.25 (m, 5H), 7.14-7.08(m, 1H), 6.56 (dt, 1H, J_(H,F(gem))=47.6 Hz, J_(H,F(vic))=4.67 Hz,),4.08 (s, 3H); EI/MS 581 m/e (M+); Calcd for C₂₁H₁₂BrCl₂F₄N₃OS: C, 43.40;H, 2.08; N, 7.23; Found: C, 43.51; H, 2.10; N, 7.11.

3-(2-Chloro-6-fluorophenyl)-5-{4-chloro-5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]thien-3-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a tan solid (71% yield): mp 82-87° C.; ¹H NMR(CDCl₃) δ 7.71 (m, 3H), 7.40-7.30 (m, 4H), 7.15-7.09 (m, 1H), 6.30 (dt,1H, J_(H,F(gem))=47.9 Hz, J_(H,F(vic))4.02 Hz), 4.01 (s, 3H); EI/MS 536m/e (M+H); Calcd for C₂₁H₁₂Cl₃F₄N₃OS: C, 46.99; H, 2.25; N, 7.83; Found:C, 47.06; H, 2.45; N, 7.70.

3-(2-Chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-3-chlorothien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white solid (72% yield): mp 135-138° C.; ¹HNMR (CDCl₃) δ 7.60 (m, 2H), 7.40-7.28 (m, 5H), 7.14-7.08 (m, 1H), 6.29(dt, 1H, J_(H,F (gem))=47.9 Hz, J_(H,F(vic))3.93 Hz), 4.08 (s, 3H);EI/MS 535 m/e (M+); Calcd for C₂₁H₁₂Cl₃F₄N₃OS: C, 46.99; H, 2.25; N,7.83; Found: C, 46.99; H, 2.31; N, 7.69.

3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a clear foam (70% yield): ¹H NMR (CDCl₃) δ 2.32(s, 3H), 4.07 (s, 3H), 6.57 (dt, 1H, J=47.9, 4.9, 4.4 Hz), 7.08-7.14 (m,1H), 7.28-7.37 (m, 4H), 7.41 (d, 3H, J=7.3 Hz); EI/MS 560 m/e (M+H);Calcd. for C₂₂H₁₅ClBrF₄N₃OS: C, 47.12; H, 2.70; N, 7.49; Found: C,47.35; H, 2.78; N, 7.36.

3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(2-chloro-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a clear oil (71% yield): ¹H NMR (CDCl₃) δ 2.32(s, 3H), 4.07 (s, 3H), 6.30 (dt, 1H, J=48.1, 4.1 Hz), 7.08-7.14 (m, 1H),7.27-7.43 (m, 7H); EI/MS 516 m/e (M+H).

3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a clear oil (44% yield): ¹H NMR (CDCl₃) δ 2.32(s, 3H), 4.06 (s, 3H), 5.03 (m, 1H), 7.08-7.14 (m, 1H), 7.29-7.37 (m,4H), 7.39-7.44 (m, 3H); EI/MS 549 m/e (M+H); Calcd. for C₂₃H₁₅ClF₇N₃OS:C, 50.24; H, 2.75; N, 7.64; Found: C, 50.36; H, 3.01; N, 7.39.

3-(2-Chloro-6-fluorophenyl)-5-(4-{4-[(2,2-dichloro-1-fluorovinyl)oxy]phenyl}-3-methylthien-2-yl)-1-methyl-1H-1,2,4-triazole

Product was isolated as a clear oil (10% yield): ¹H NMR (CDCl₃) δ 2.31(s, 3H), 4.06 (s, 3H), 7.08-7.17 (m, 3H), 7.29-7.37 (m, 2H), 7.38-7.42(m, 3H); EI/MS 512 m/e (M+H).

3-(2-Chloro-6-fluorophenyl)-5-{4-[4-(2,2-dichloro-1,1-difluoroethoxy)phenyl]-3-methylthien-2-yl}-1-methyl-1H-1,2,4-triazole

Product was isolated as a white waxy solid (53% yield): mp 114-116° C.;¹H NMR (CDCl₃) δ 2.32 (s, 3H), 4.07 (s, 3H), 5.95 (t, 1H, J=4.8, 4.4Hz), 7.08-7.14 (m, 1H), 7.28-7.38 (m, 4H), 7.39-7.42 (m, 3H); EI/MS 532m/e (M+H).

Example 8

3-(2-Chloro-6-fluorophenyl)-5-[3-methyl-4-bromo-5-(4-trifluoromethoxyphenyl)2-thienyl]-1-ethyl-[1,2,4]-triazole

Methyl-N-{[3-methyl-4-bromo-5-(4-trifluoromethoxyphenyl)-2-thienyl]-carbonyl}-2-fluoro-6-chlorobenzenecarbimidothioate(0.85 g, 1.5 mmol) and ethylhydrazine oxalate (0.90 g, 6 mmol) werecombined in toluene (5 mL) and stirred 64 h at 25° C. and heated toreflux for 18 h. The reaction mixture was diluted with ether and washedwith 0.1 M hydrochloric acid and brine, dried over anhydrous magnesiumsulfate and concentrated to a crude pale yellow oil. Chromatography(silica gel, 10% ethylacetate/hexane) afforded the product as a clearoil (0.250 mg, 30%): ¹H NMR (CDCl₃) δ 7.73 (2H, d), 7.0-7.5 (5H, m), 4.3(2H, q), 2.40 (3H, s), 1.55 (3H, t); EI/MS 546 m/e (M+).

Example 9

5-{5-Bromo-4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole

Bromine (0.03 g, 0.2 mmol) in acetic acid (0.5 mL) was added dropwise toa solution of5-{4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthien-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole(0.1 g, 0.2 mmol) in acetic acid (1 mL) at 0° C. The reaction wasallowed to warm to 25° C. and stirred for 50 h. The reaction mixture wasmade basic with saturated aq NaHCO₃ (30 mL) and extracted with ether(3×30 mL). The combined ether extracts were washed with brine, driedover sodium sulfate, filtered, and the solvent removed under reducedpressure to give crude product. Column chromatography gave the productas a clear oil (88 mg, 77%): ¹H NMR (CDCl₃) δ 2.19 (s, 3H), 4.06 (s,3H), 6.58 (dt, 1H, J=47.6, 5.1, 4.0, 4.4 Hz), 7.08-7.14 (m, 1H),7.29-7.40 (m, 6H), EI/MS 636 m/e (M+H).

Example 10

The compounds identified in the following Tables 1-4 were prepared usingthe procedures illustrated in the foregoing examples, and the compoundswere tested against tobacco budworm, beet armyworm, cabbage looper,cotton aphid, two-spotted spider mite, and sweetpotato whitefly usingprocedures described hereinafter.

TABLE 1

R¹ R² Y Ar TBW BAW CL CA SM WF Cl Cl Cl

G A E C G C Cl Cl Cl

B D F E G F Cl Cl Cl

G A A C G E Cl Cl Cl

G G D C A C CH₃ H Cl

D A B A A G CH₃ Br Cl

G A G A A G Cl H F

B A B F F G Cl H F

G A B G G G Cl H F

G B A D F G CH₃ H F

F A A A A F Cl H F

G A A G F G H Br Cl

G A A G A F Cl H Cl

A A A C A G Cl H Cl

A A A D A F Cl H Cl

G A D F G G Cl H Cl

G A D B A G Cl Br Cl

D B A A C F Cl H Cl

A A A B A G CH₃ H Cl

G A D B G F CH₃ H Cl

D A A A A D Cl Br Cl

F A A A G G Cl Br Cl

F D A A F G CH₃ H Cl

G D A B A G CH₃ H Cl

G G A B A F CH₃ H Cl

F D A B A G CH₃ H Cl

F D A A A A CH₃ H Cl

F A A C A G CH₃ H Cl

B A A A A G CH₃ H Cl

F A A C A G CH₃ H Cl

D A A D A G CH₃ H Cl

G A A B B G CH₃ H Cl

G B A D C G CH₃ H Cl

F F G B C G CH₃ H Cl

G D B D A CH₃ H Cl

A A A D A F CH₃ H Cl

A A A A B E CH₃ H Cl

A A A B A F Cl H Cl

A A A E C G

TABLE 2

R¹ R² Y Ar TBW BAW CL CA SM WF CH₃ H Cl

D A A A A A CH₃ H Cl

G D G A B G CH₃ H Cl

G B F A A F CH₃ H Cl

G B A B G A CH₃ H Cl

G D G B E G CH₃ H Cl

G D A A G G CH₃ H Cl

G B G B F CH₃ Br Cl

G A A B F D CH₃ CH₃ Cl

G A A A A E CH₃ Cl Cl

B A A C F G H H Cl

F A A D G G H H Cl

A A A F G G H H F

D G A A G G H Br Cl

B A A B A G CH₃ H Cl

G G B A G B H H F

G G A C G G H Br Cl

A A A G G G H H Cl

G F A A A G H CH₃ Cl

A A A A A G CH₃ H Cl

G G A A F B CH₃ H Cl

F A A A A A CH₃ H Cl

G A A A G A CH₃ H Cl

A A A B A A CH₃ H Cl

G G A A B A CH₃ H Cl

A A A D B A CH₃ H Cl

A A A B A A CH₃ H Cl

G A F A G A CH₃ H Cl

A A A B A A CH₃ H Cl

G G A B A G CH₃ H Cl

B A A A A G CH₃ H Cl

G G D C G F CH₃ H Cl

F D A A F F CH₃ H Cl

D G A A G G CH₃ H Cl

F G G A G G CH₃ H Cl

F A A A A A CH₃ H Cl

G B B C D F CH₃ H Cl

G D A B G G CH₃ H Cl

F G A B F F CH₃ H Cl

G G A A F E CH₃ H Cl

F G A A A G CH₃ H Cl

G F A A A G CH₃ H Cl

G G A B B F CH₃ H Cl

F G D B B F H H Cl

F G B G G H Cl Cl

G A A A A G H Cl Cl

A A A F A G H H Cl

D A A C C F H Cl Cl

F G A C G G H Cl Cl

G G A A A G H Cl Cl

G G B A G H H Cl

F G A B A F H Cl Cl

F A A F G F H CH₃ Cl

A A A F A G H CH₃ Cl

G A D B A C H Cl Cl

F A A F A F H Cl Cl

F A A F A H CH₃ Cl

G D G C A F H CH₃ Cl

G G A A A F H CH₃ Cl

G A A B A F H CH₃ Cl

F A A F A G H CH₃ Cl

G F A B G G CH₃ H Cl

B A A A F A CH₃ CH₃ Cl

D A A B F G CH₃ CH₃ Cl

G A A B H CH₃ Cl

G A A F B G H H Cl

G G F C F G CH₃ H Cl

G G A B F F H CH₃ Cl

F G G D G G CH₃ CH₃ Cl

G A A A C F CH₃ H Cl

A A A A A A Cl H Cl

B B A B C A Cl H Cl

A B A C C E CH₃ H Cl

G B A C E A CH₃ H F

G G A E G G Cl H Cl

F A A B A A CH₃ H Cl

A A A B F A CH₃ H Cl

A A A C B A CH₃ H Cl

F A F B F F CH₃ H Cl

A A A C E A CH₃ C₂H₅ Cl

B A A B G G CH₃ CH₃ Cl

A A A E G G CH₃ C₂H₅ Cl

F A A B G F

TABLE 3

R¹ R² Y Ar TBW BAW CL CA SM WF CH₃ H Cl

A A A A A A CH₃ H Cl

D D G D A F CH₃ Br Cl

G E G A G G CH₃ Cl Cl

G A G A G F CH₃ H Cl

E A A B A A CH₃ H Cl

B A A A G A CH₃ H Cl

B A A B C A CH₃ H Cl

A A A D A A CH₃ Br Cl

F A A B G F

TABLE 4

R¹ R² R³ Y Ar TBW BAW CL CA SM WF CH₃ Br Et Cl

G A A C C F TBW refers to activity at 400 ppm against tobacco budworm,BAW refers to activity at 400 ppm against beet armyworm, CL refers toactivity at 400 ppm against cabbage looper, CA refers to activity at 50ppm against cotton aphid, SM refers to activity at 2.5 ppm againsttwo-spotted spider mite, WF refers to activity at 200 ppm againstwhitefly.

In each case the rating scale is as follows

% Control Rating  90-100 A 80-89 B 70-79 C 60-69 D 50-59 E less than 50F Inactive G

Insecticide and Miticide Utility

The compounds of the invention are useful for the control of insects andmites. Therefore, the present invention also is directed to a method forinhibiting an insect or mite which comprises applying to a locus of theinsect or mite an insect- or mite-inhibiting amount of a compound offormula (1).

The compounds are useful for reducing populations of insects and mitesand are useful in a method of inhibiting an insect or mite populationwhich comprises applying to a locus of the insect or mite an effectiveinsect- or mite-inactivating amount of a compound of formula (1). The“locus” of insects or mites is a term used herein to refer to theenvironment in which the insects or mites live or where their eggs arepresent, including the air surrounding them, the food they eat, orobjects which they contact. For example, insects or mites which eat orcontact edible or ornamental plants can be controlled by applying theactive compound to plant parts such as the seed, seedling, or cuttingwhich is planted, the leaves, stems, fruits, grain, or roots, or to thesoil in which the roots are growing. It is contemplated that thecompounds might also be useful to protect textiles, paper, stored grain,seeds, domesticated animals, buildings or human beings by applying anactive compound to or near such objects. The term “inhibiting an insector mite” refers to a decrease in the numbers of living insects or mites,or a decrease in the number of viable insect or mite eggs. The extent ofreduction accomplished by a compound depends, of course, upon theapplication rate of the compound, the particular compound used, and thetarget insect or mite species. At least an inactivating amount should beused. The terms “insect-inactivating amount” and “mite-inactivatingamount” are used to describe the amount, which is sufficient to cause ameasurable reduction in the treated insect or mite population. Generallyan amount in the range from about 1 to about 1000 ppm by weight activecompound is used. For example, insects and mites which can be inhibitedinclude, but are not limited to:

Lepidoptera—Heliothis spp., Helicoverpa spp., Spodoptera spp., Mythimnaunipuncta, Agrotis ipsilon, Earias spp., Euxoa auxiliaris, Trichoplusiani, Anticarsia gemmatalis, Rachiplusia nu, Plutella xylostella, Chilospp., Scirpophaga incertulas, Sesamia inferens, Cnaphalocrocismedinalis, Ostrinia nubilalis, Cydia pomonella, Carposina niponensis,Adoxophyes orana, Archips argyrospilus, Pandemis heparana, Epinotiaaporema, Eupoecilia ambiguella, Lobesia botrana, Polychrosis viteana,Pectinophora gossypiella, Pieris rapae, Phyllonorycter spp., Leucopteramalifoliella, Phyllocnisitis citrella

Coleoptera—Diabrotica spp., Leptinotarsa decemlineata, Oulema oryzae,Anthonomus grandis, Lissorhoptrus oryzophilus, Agriotes spp., Melanotuscommunis, Popillia japonica, Cyclocephala spp., Tribolium spp.

Homoptera—Aphis spp., Myzus persicae, Rhopalosiphum spp., Dysaphisplantaginea, Toxoptera spp., Macrosiphum euphorbiae, Aulacorthum solani,Sitobion avenae, Metopolophium dirhodum, Schizaphis graminum,Brachycolus noxius, Nephotettix spp., Nilaparvata lugens, Sogatellafurcifera, Laodelphax striatellus, Bemisia tabaci, Trialeurodesvaporariorum, Aleurodes proletella, Aleurothrixus floccosus,Quadraspidiotus perniciosus, Unaspis yanonensis, Ceroplastes rubens,Aonidiella aurantii

Hemiptera—Lygus spp., Eurygaster maura, Nezara viridula, Piezodorusguildingi, Leptocorisa varicornis

Thysanoptera—Frankliniella occidentalis, Thrips spp., Scirtothripsdorsalis

Isoptera—Reticulitermes flavipes, Coptotermes formosanus

Orthoptera—Blattella germanica, Blatta orientalis, Gryllotalpa spp.

Diptera—Liriomyza spp., Musca domestica, Aedes spp., Culex spp.,Anopheles spp.

Hymenoptera—Iridomyrmex humilis, Solenopsis spp., Monomorium pharaonis,Atta spp., Pogonomyrmex spp., Camponotus spp.

Siphonaptera—Ctenophalides spp., Pulex irritans

Acarina—Tetranychus spp., Panonychus spp., Eotetranychus carpini,Phyllocoptruta oleivora, Aculus pelekassi, Brevipalpus phoenicis,Boophilus spp., Dermacentor variabilis, Rhipicephalus sanguineus,Amblyomma americanum, Ixodes spp., Notoedres cati, Sarcoptes scabiei,Dermatophagoides spp.

Insecticidal Test for Tobacco Budworm (Heliothis virescens) BeetArmyworm (Spodoptera exizua), and Cabbage Looper (Trichoplusia ni).

To prepare test solution, the test compound was formulated at 400 ppm in7.5 mL of 2 acetone: 1 tap water. 250 μL of the test solution waspipetted upon the surface of 8 mL of lepidopteran diet (modified Shorey)contained in each of five one-ounce plastic cups (one cup=1replication). A second-instar beet armyworm was placed upon the treateddiet in each cup once the solvent had air-dried. The solutions remainingafter completing applications to the one-ounce cups were then used asleaf-dip solutions for 3.5 cm leaf discs cut from cabbage leaves andcotton cotyledons. Five discs of each type of plant were dipped untilthoroughly coated into each rate of each compound (=5 replications ofeach treatment). After air-drying, the treated leaf discs were placedindividually into one-ounce plastic cups. Each dried, treated cottoncotyledon disc was infested with a 2^(nd) instar tobacco budworm larva,and each cabbage leaf disc was infested with a 2^(nd) instar cabbagelooper larva. Cups containing the treated substrates and larvae werecapped and then held in a growth chamber at 25° C., 50-55% RH, and 14 hrlight: 10 hr dark for 5 days. The number of dead insects of 5 perspecies per treatment was then determined and the results are given inTables 1-4.

Insecticidal Test for Cotton Aphid (Aphis gossypii)

To prepare spray solutions, 1 mg of each test compound was dissolvedinto 1 mL of a 90:10 acetone:ethanol solvent. This 1 mL of chemicalsolution was added to 19 mL of water containing 0.05% Tween 20surfactant to produce a 50 ppm spray solution.

Squash cotyledons were infested with cotton aphid (all life stages)16-20 hours prior to application of spray solution. The solution wassprayed on both sides of each infested squash cotyledon (0.5 mL×2 eachside) with a sweeping action until runoff. The plants were allowed toair dry and held for 3 days in a controlled room at 26° C. and 40% RHafter which time the test was graded. Grading was by actual count usinga dissecting microscope and comparison of test counts to the untreatedcheck. Results are given in Tables 1-4 as percent control based onpopulation reduction versus the untreated.

Insecticidal Test for Two-Spotted Spider Mite (Tetranychus urticae)

Ovicide Method:

Ten adult female two-spotted spider mites were placed on eight 2.2 cmleaf discs of cotton leaf, allowed to oviposit over 24 hours, andthereafter removed. The leaf discs were sprayed with 100 ppm testsolutions using a hand syringe, then allowed to dry with sixteen discsleft untreated as a negative control. Discs were placed on an agarsubstrate and held at 24° C. and 90% RH for 6 days. Percent controlbased on the number of hatched larvae on treated discs and the number onuntreated discs is reported in Tables 1-4.

Insecticidal Test for Sweetpotato Whitefly (Bemisia tabacia)

Four mg of each test compound was dissolved by adding 4 mL of a 90:10acetone:ethanol solvent mixture to the vial containing the samplecompound. This solution was added to 16 mL of water containing 0.05%Tween 20 surfactant to produce 20 mL of an 200 ppm spray solution.

Five-week-old cotton plants reared in a greenhouse were stripped of allfoliage except for the two uppermost true leaves that were greater than5 cm in diameter. These plants were then placed into a laboratory colonyof whiteflies for two days for oviposition by the colony females. Allwhiteflies were then removed from the test plants with pressurized air.The spray solution was then applied to the test plants with a hand-heldsyringe fitted with hollow cone nozzle. One mL spray solution wasapplied to each leaf top and bottom for a total of 4 mL per plant. Fourreplications of each test compound utilized a total of 16 mL spraysolution. Plants were air dried and then placed in a holding chamber(28° C. and 60% RH) for 13 days. Compound efficacy was evaluated bycounting, under an illuminated magnifying glass, the number of largenymphs (3rd-4th instar) per leaf.

Percent control based on reduction of large nymphs of a test compoundcompared to solution-only (no test compound) sprayed plants is reportedin Tables 1-4.

Compositions

The compounds of this invention are applied in the form of compositionswhich are important embodiments of the invention, and which comprise acompound of this invention and a phytologically-acceptable inertcarrier. The compositions are either concentrated formulations which aredispersed in water for application, or are dust or granular formulationswhich are applied without further treatment. The compositions areprepared according to procedures and formulae which are conventional inthe agricultural chemical art, but which are novel and important becauseof the presence therein of the compounds of this invention. Somedescription of the formulation of the compositions will be given,however, to assure that agricultural chemists can readily prepare anydesired composition.

The dispersions in which the compounds are applied are most oftenaqueous suspensions or emulsions prepared from concentrated formulationsof the compounds. Such water-soluble, water-suspendable or emulsifiableformulations are either solids, usually known as wettable powders, orliquids usually known as emulsifiable concentrates or aqueoussuspensions. Wettable powders, which may be compacted to form waterdispersible granules, comprise an intimate mixture of the activecompound, an inert carrier, and surfactants. The concentration of theactive compound is usually from about 10% to about 90% by weight. Theinert carrier is usually chosen from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among the sulfonated lignins, thecondensed naphthalenesulfonates, the naphthalenesulfonates, thealkylbenzenesulfonates, the alkyl sulfates, and nonionic surfactantssuch as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenientconcentration of a compound, such as from about 50 to about 500 gramsper liter of liquid, equivalent to about 10% to about 50%, dissolved inan inert carrier which is either a water miscible solvent or a mixtureof water-immiscible organic solvent and emulsifiers. Useful organicsolvents include aromatics, especially the xylenes, and the petroleumfractions, especially the high-boiling naphthalenic and olefinicportions of petroleum such as heavy aromatic naphtha. Other organicsolvents may also be used, such as the terpenic solvents including rosinderivatives, aliphatic ketones such as cyclohexanone, and complexalcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiableconcentrates are chosen from conventional nonionic surfactants, such asthose discussed above.

Aqueous suspensions comprise suspensions of water-insoluble compounds ofthis invention, dispersed in an aqueous vehicle at a concentration inthe range from about 5% to about 50% by weight. Suspensions are preparedby finely grinding the compound, and vigorously mixing it into a vehiclecomprised of water and surfactants chosen from the same types discussedabove. Inert ingredients, such as inorganic salts and synthetic ornatural gums, may also be added, to increase the density and viscosityof the aqueous vehicle. It is often most effective to grind and mix thecompound at the same time by preparing the aqueous mixture, andhomogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

The compounds may also be applied as granular compositions, which areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the compound,dispersed in an inert carrier which consists entirely or in large partof clay or a similar inexpensive substance. Such compositions areusually prepared by dissolving the compound in a suitable solvent andapplying it to a granular carrier which has been pre-formed to theappropriate particle size, in the range of from about 0.5 to 3 mm. Suchcompositions may also be formulated by making a dough or paste of thecarrier and compound and crushing and drying to obtain the desiredgranular particle size.

Dusts containing the compounds are prepared simply by intimately mixingthe compound in powdered form with a suitable dusty agriculturalcarrier, such as kaolin clay, ground volcanic rock, and the like. Dustscan suitably contain from about 1% to about 10% of the compound.

It is equally practical, when desirable for any reason, to apply thecompound in the form of a solution in an appropriate organic solvent,usually a bland petroleum oil, such as the spray oils, which are widelyused in agricultural chemistry.

Insecticides and acaricides are generally applied in the form of adispersion of the active ingredient in a liquid carrier. It isconventional to refer to application rates in terms of the concentrationof active ingredient in the carrier. The most widely used carrier iswater.

The compounds of the invention can also be applied in the form of anaerosol composition. In such compositions the active compound isdissolved or dispersed in an inert carrier, which is apressure-generating propellant mixture. The aerosol composition ispackaged in a container from which the mixture is dispensed through anatomizing valve. Propellant mixtures comprise either low-boilinghalocarbons, which may be mixed with organic solvents, or aqueoussuspensions pressurized with inert gases or gaseous hydrocarbons.

The actual amount of compound to be applied to loci of insects and mitesis not critical and can readily be determined by those skilled in theart in view of the examples above. In general, concentrations from 10ppm to 5000 ppm by weight of compound are expected to provide goodcontrol. With many of the compounds, concentrations from 100 to 1500 ppmwill suffice.

The locus to which a compound is applied can be any locus inhabited byan insect or mite, for example, vegetable crops, fruit and nut trees,grape vines, ornamental plants, domesticated animals, the interior orexterior surfaces of buildings, and the soil around buildings.

Because of the unique ability of insect and mite eggs to resist toxicantaction, repeated applications may be desirable to control newly emergedlarvae, as is true of other known insecticides and acaricides.

What is claimed is:
 1. A compound of the formula (1)

wherein X and Y independently represent Cl or F; R¹ represents CH₃; R²represent H, C₁-C₆ alkyl or halogen; R³ represents C₁-C₃ alkyl; R⁴represents C₁-C₆ haloalkoxy; R⁵ represents H, or halogen; or aphytologically acceptable acid addition salt thereof.
 2. A compound ofclaim 1 in which R³ is CH₃.
 3. A compound of claim 1 in which X is F andY is Cl.
 4. A compound of claim 1 in which R² is H or CH₃.
 5. A compoundof claim 1 in which R⁵ is H, F, or Cl.
 6. A composition for controllinglepidoptera, coleoptera, mites and other sucking pests which comprises acompound of the formula (1)

wherein X and Y independently represent Cl or F; R¹ represents CH₃; R²represent H, C₁-C₆ alkyl or halogen; R³ represents C₁-C₃ alkyl; R⁴represents C₁-C₆ haloalkoxy; R⁵ represents H, or halogen; or aphytologically acceptable acid addition salt thereof in comination witha phytologically-acceptable carrier.
 7. A composition of claim 6 inwhich R³ is CH₃.
 8. A composition of claim 6 in which X is F and Y isCl.
 9. A composition of claim 6 in which R² is H or CH₃.
 10. Acomposition of claim 6 in which R⁵ is H, F, or Cl.
 11. A method ofcontrolling lepidoptera, coleoptera, mites and other sucking pests whichcomprises applying to a locus where control is desired a lepidoptera-,coleoptera-, mite- or other sucking pest-inactivating amount of acompound of the formula (1)

wherein X and Y independently represent Cl or F; R¹ represents CH₃; R²represent H, C₁-C₆ alkyl or halogen; R³ represents C₁-C₃ alkyl; R⁴represents C₁-C₆ haloalkoxy; R⁵ represents H, or halogen; or aphytologically acceptable acid addition salt thereof in comination witha phytologically-acceptable carrier.
 12. A method of claim 11 in whichR³ is CH₃.
 13. A method of claim 11 in which X is F and Y is Cl.
 14. Amethod of claim 11 in which R² is H or CH₃.
 15. A method of claim 11 inwhich R⁵ is H, F, or Cl.